David N. Velazquez-Martinez - Academia.edu (original) (raw)
Papers by David N. Velazquez-Martinez
Progressive ratio (PR) schedules had been widely used to study motivation to work for a reinforce... more Progressive ratio (PR) schedules had been widely used to study motivation to work for a reinforcer. After a post-reinforcer pause, subjects engage pressing a lever until a reinforcer is obtained. However, the discrete nature of lever presses allows alternative behaviors during inter-response time and had lead to the suggestion of several behavioral categories to explain pauses and work time. A progressive hold-down (PH) is incompatible with alternative responses and may allow a precise estimation of work time. Performance of rats trained in both PR and PH that received sucrose or intracranial self-stimulation (ICSS) as reinforcer were compared. We observed that rats mastered the PR and PH schedules. Post-reinforcer pauses, work time and inter-reinforcer time increased as a function of the response or hold requirement. However, rat’s performance suggest that the PH progression may be experienced by the rats as easier that the PR progression. Elimination of consummatory behavior with ...
Frontiers in Behavioral Neuroscience, 2022
Rats work very hard for intracranial self-stimulation (ICSS) and tradeoff effort or time allocati... more Rats work very hard for intracranial self-stimulation (ICSS) and tradeoff effort or time allocation for intensity and frequency parameters producing a sigmoidal function of the subjective reward magnitude of ICSS. Previous studies using electrical intracranial stimuli (ICS) as a discriminative cue focused on estimating detection thresholds or on the discrimination between intensities. To our knowledge, there is no direct comparison of the reinforcer tradeoff functions with the discriminative functions. Rats were trained to press and hold the lever for ICSS using the maximum reinforcing intensity below motor alterations or avoidance behavior. First, rats were trained to hold the lever for 1 s; after stability, they undergo trials where intensity or frequency was decreased on 0.1 log step. Thereafter, they undergo further training with a hold of 2 and later of 4 s to determine tradeoff with intensity or frequency. The same rats were trained on a discrimination task where the previousl...
Revista Mexicana de Análisis de la Conducta; Vol 7, No 2 (1981); 159-164, Sep 23, 2011
The performonce of an instrumental response, maintained under o fixed-interval schedule, was stud... more The performonce of an instrumental response, maintained under o fixed-interval schedule, was studied 30 sec., 40 min., 4 hr. and 8 hs.. afterr administering holoperidol, in rats. A marked reduction of operant responding was seen after the first two periods, and a behavioral recovery, of about 50% of control response rates, during the last two periods. A marked decrement in food and water intake was olso seen after the first three periods, and a near-normal intake 8 hr. after the treatment It is known that the administration of kaloperidol produces a specific and signiflcant reductton of acetylcitoline levels in tite caudate nucleus. Token togetiter, these data give fitrther support to the hypotitesis The performance of instrumental tasks is critically dependent upon the cholinergic activity of the caudate nucleus.
Revista Mexicana de Análisis de la Conducta; Vol 12, No 2 (1986): SEPTIEMBRE 1986; 157-167, May 23, 2011
En el presente trabajo se presenta una revision de los trabajos que analizan las propiedades diso... more En el presente trabajo se presenta una revision de los trabajos que analizan las propiedades disociativas del alcohol asi como de aquellos en los que se utiliza la administracion de este como estimulo discriminativo. Tambien se presenta un resumen de los resultados obtenidos cuando se realizan pruebas de generalizacion de estimulos con sujetos entrenados previamente a discriminar la administracion del alcohol de alguna otra condicion farmacologica. De los trabajos revisados se puede concluir que el alcohol posee efectos disociativos y que su administracion puede ser utilizada como senal discriminativa; sin embargo, estos efectos son singulares ya que la mayoria de las drogas evaluadas en las pruebas de generalizacion de estimulos no se generalizan con la senal discriminativa del alcohol. La excepcion la constituyen los barbituricos (aunque se ha demostrado que los sujetos pueden diferenciar entre la administracion del alcohol y los barbituricos) y el 3-carboxisalsolinol, que es un producto metabolico del alcohol. Finalmente, se han observado diferencias en el grado de disociacion dependiendo de si el entrenamiento inicial se realizo bajo los efectos del alcoholo de alguna otra condicion farmacologica
Proceedings of the Western Pharmacology Society
Proceedings of the Western Pharmacology Society, 1998
Proceedings of the Western Pharmacology Society, 1998
Revista Mexicana de Análisis de la Conducta, 2011
Journal of Neural Transplantation and Plasticity, 1992
Revista Mexicana de Análisis de la Conducta, 2011
... O'Dell, LE, Sussman, AN, Meyer, KL, Neisewander, JL Behavioral effects of psychomotor sti... more ... O'Dell, LE, Sussman, AN, Meyer, KL, Neisewander, JL Behavioral effects of psychomotor stimulant infusions into amygdaloid nuclei. Neuropsychopharmacology 1999.20(6): 591-602. Orozco, G, López-Cabrera, M., Velazquez-Martinez, DN Control de estímu-los con fármacos ...
Pharmacological reports : PR
Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the mesolimbic dopamine... more Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the mesolimbic dopamine (DA) system. The behavioral effects of AMPH are largely mediated by increased DA neurotransmission in the nucleus accumbens. However, there is evidence that serotonin (5-hydroxytryptamine - 5-HT) systems may regulate forebrain DA function. We examined the role of 5-HT1B receptors on the discriminative stimulus properties of AMPH using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received the administration of AMPH (1.0 mg/kg) before a 10 min period of access to saccharin solution and followed by an injection of LiCl; on alternate days, rats received saline before and after the access to saccharin solution. In generalization and combination tests, the training dose of AMPH was substituted by 5-HT1B receptor ligands RU24969 (5-HT1B agonist: 0.1, 0.3 and 1.0 mg/kg), CP94253 (5-HT1B agon...
Psychopharmacology, 1996
Acute treatment with antidepressant drugs is known to increase the mean interresponse time (IRT) ... more Acute treatment with antidepressant drugs is known to increase the mean interresponse time (IRT) in the IRT>72-s schedule of reinforcement. In order to examine the possibility that this effect may reflect an action of the antidepressants on timing processes, we tested the effects of two antidepressants, desipramine and fluvoxamine, on behaviour maintained under two other timing schedules in rats. In the fixed-interval peak procedure (fixed-interval 30-s), acute treatment with desipramine (8mgkg-~) reduced response rate, whereas acute treatment with fluvoxamine (8 mg kg-a) increased it. Neither drug significantly altered the time to attainment of peak response rate or the Weber fraction. In the interval bisection task (standard durations 2 s and 8 s), the bisection point was not significantly altered by acute treatment with either drug. Chronic treatment with desipramine (8 mg kg-t b.d.) had no effect on any of the indices of timing under either schedule. Chronic treatment with fluvoxamine (8 mg kg-1 b.d.) reduced the time to attainment of peak response rate but had no effect on the Weber fraction under the fixed-interval peak procedure, and did not alter the bisection point or Weber fraction under the interval bisection procedure. The failure of desipramine and fluvoxamine to increase the time to peak response rate or the bisection point at doses that significantly altered operant response rate suggests that the effect of these drugs on IRT schedule performance is unlikely to reflect an interaction with timing processes.
Psychopharmacology, 2002
Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive beh... more Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size and delay) has been proposed as a model of "impulsive choice" in animals. Objective: A quantitative method was used to analyse inter-temporal choice in rats with lesions of the OPFC and sham-lesioned control rats. Methods: Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC (0.1 M, 0.5 l; two injections in each hemisphere), or sham lesions (injections of the vehicle). They were trained to press two levers (A and B) for sucrose reinforcement (0.6 M) in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of 50 l of the sucrose solution after a delay d A ; a press on B resulted in delivery of 100 l of the same solution after a delay d B. d B was increased progressively across successive blocks of six trials in each session, while d A was manipulated systematically across phases of the experiment. The indifference delay, d B(50) (value of d B corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of d B(50) versus d A were derived, and the parameters of the function compared between the groups. The locations of the lesions were verified histologically at the end of the experiment. Results: In both groups, d B(50) increased linearly with d A (r 2 >0.98 in each case). The slope of the function was significantly steeper in the lesioned group than the sham-lesioned group, whereas the intercept did not differ significantly between the groups. The brains of the lesioned rats showed extensive atrophy/gliosis of the OPFC, with sparing of the dorsolateral prefrontal cortex. Conclusions: The results indicate that lesions of the OPFC can alter inter-temporal choice, either promoting or suppressing "impulsive choice", depending upon the relative sizes and delays of the two choice alternatives. Theoretical analysis based on a quantitative model of inter-temporal choice indicates that the pattern of effect of the OPFC lesion is likely to reflect two actions: (i) an increase in the rate of time discounting; (ii) an increase in sensitivity to the ratio of the sizes of two reinforcers.
Psychopharmacology, 1995
This experiment examined the effect of destroying central noradrenergic neurones, using the selec... more This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) on the acquisition and performance of discrimination between two time intervals. Rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and lever B following an 8-s presentation of the same stimulus. Both groups acquired the discrimination (> 90% correct choices) within 15 sessions; however, the DSP4-treated group showed significantly slower acquisition than the control group. When stable performance had been attained, 'probe' trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. Neither the bisection point (duration corresponding to 50% choice of lever B) nor the Weber fraction differed significantly between the DSP4-treated and control groups. The levels of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the levels of dopamine and 5-hydroxytryptamine were not altered. The results indicate that noradrenaline depletion induced by DSP4 retarded the acquisition of temporal discrimination, but did not impair steady-state discriminative precision.
Psychopharmacology, 1996
This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTe... more This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule. Rats received either injections of 5,7dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for a sucrose reinforcer. Training sessions consisted of 40, 50-s trials in which reinforcers were available on a variable-interval 25-s schedule; in the first 25 s of each trial, reintbrcers were only available for responses on lever A, whereas in the last 25 s reinforcers were available only tbr responses on lever B. Data were collected from probe trials (/bur per session) in which no reinforcers were delivered, during the last ten of 50 training sessions. Both groups showed decreasing response rates on lever A and increasing response rates on lever B as a function of time from the onset of the trial. Response rate on lever B, expressed as a percentage of overall response rate, could be described by a two-parameter logistic function; neither the indifference point (i.e. the time corresponding to 50% responding on lever B) nor the slope of the function differed between the two groups. However, the lesioned group showed a higher rate of switching between response alternatives than the sham-lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results confirm previous findings that behaviour in timing
Psychopharmacology, 2004
Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive beh... more Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size and delay) has been proposed as a model of "impulsive choice" in animals. We recently found that destruction of the OPFC disrupted inter-temporal choice in rats. It is not known whether the dopaminergic projection to the OPFC contributes to the regulation of inter-temporal choice. Objective: A quantitative method was used to compare intertemporal choice in rats whose OPFC had been depleted of dopamine with that of sham-lesioned control rats. Methods: Under halothane anaesthesia, rats received injections of 6-hydroxydopamine into the OPFC (2 mg ml 1 , 0.5 ml, two injections in each hemisphere), or sham lesions (injections of the vehicle). They were trained to press two levers (A and B) for sucrose reinforcement (0.6 M) in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of 50 ml of the sucrose solution after a delay d A ; a press on B resulted in delivery of 100 ml of the same solution after a delay d B. d B was increased progressively across successive blocks of six trials in each session, while d A was manipulated systematically across phases of the experiment. The indifference delay, d B(50) (value of d B corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of d B(50) versus d A were derived, and the parameters of the function compared between the groups. Concentrations of monoamines in the OPFC were determined by highperformance liquid chromatography at the end of the experiment. Results: In both groups, d B(50) increased linearly with d A (r 2 >0.9 in each case). The slope of the function was significantly steeper in the lesioned group than the sham-lesioned group, whereas the intercept did not differ significantly between the groups. When delays of 4 or 8 s were imposed on the smaller reinforcer, the lesioned rats showed greater tolerance of delay to the larger reinforcer (i.e. they exhibited longer values of d B(50)) than the sham-lesioned rats. Dopamine, noradrenaline and 5-hydroxytryptamine levels in the OPFC of the lesioned group were 20, 75 and 98% of those of the shamlesioned group. Conclusions: The results indicate that dopaminergic afferents to the OPFC contribute to the regulation of inter-temporal choice behaviour due to their role in determining organisms' sensitivity both to reinforcer size and to delay of reinforcement.
Pharmacology Biochemistry and Behavior, 2002
Interval timing behaviour is revealed by prospective, immediate and retrospective timing schedule... more Interval timing behaviour is revealed by prospective, immediate and retrospective timing schedules. Prospective timing tasks are used to study intertemporal choice (choice between outcomes occurring after different delays), immediate timing tasks to study temporal differentiation (temporal regulation of the animal's behaviour) and retrospective timing tasks to study temporal discrimination (discrimination between the durations of external events). Central 5-hydroxytryptamine (5-HT) depletion promotes preference for small early reinforcers over large delayed reinforcers, possibly by facilitating the time-dependent degradation of reinforcer value. Central 5-HT depletion retards the learning of temporal differentiation, and increases the variability of timing in some immediate timing tasks; however, it does not impede (in some cases it facilitates) the acquisition of temporal discrimination. Attempts to ascribe all the effects of 5-HT depletion on timing to a single behavioural process have been unsuccessful, although disinhibition of switching between operant responses may account for some of the findings. Acute treatment with drugs affecting 5-HTergic mechanisms alters timing behaviour in qualitatively different ways in different timing schedules, casting doubt on the idea that the effects of these drugs are mediated by interaction with a unitary timing process. The receptors that mediate 5-HT's putative involvement in interval timing behaviour remain to be identified.
Pharmacology Biochemistry and Behavior, 2003
Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine... more Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine, 5-HT) agonist that has affinity for 5-HT(1A/1B/2C) receptors. Unlike other anxiolytics such as 5-HT receptor agonists, INDO may not share tolerance or dependency with the benzodiazepine anxiolytics. It has been reported that the discriminative stimulus properties of 5-HT(1A/1B/2C) agonists, but not those of 5-HT(3/4) agonists, generalize to INDO. Therefore, the aim of the present study was to obtain further evidence on the differential involvement of 5-HT(1A/1B/2C) receptors in the discriminative stimulus properties of INDO by evaluating its interactions with antagonists of the 5-HT(1A), 5-HT(1B), 5-HT(2C), and 5-HT(3/4) receptor subtypes. Rats were trained to discriminate INDO from saline in a conditioned taste aversion paradigm. For Group D(+)S(-), administration of INDO signalled that saccharin flavour was followed by LiCl, while injection of vehicle signalled safe consumption of saccharin solution. Group D(-)S(+) had the contingencies reversed. After this training, rats had generalization tests where INDO administration was preceded by different doses of the following antagonists: WAY100635 (5-HT(1A)), NAN190 (5-HT(1A)), methiothepin (5-HT(1A/1B/2C)), GR127935 (5-HT(1B/1D)), ketanserin (5-HT(2A/2C)), ritanserin (5-HT(2C/2A)), mesulergine (5-HT(2C/2A)), metergoline (5-HT(2C/2A)), SB206553 (5-HT(2B/2C)), and tropisetron (5-HT(3/4)). In Group D(+)S(-), the order of potency to block the discriminative stimulus properties of INDO was WAY100635>ketanserin>ritanserin>GR127935>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190, while in Group D(-)S(+), the order was WAY100635>GR127935>ketanserin>ritanserin>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190. Tropisetron did not produce any alteration of the discriminative control by INDO. These results suggest that the discriminative signal of INDO is mediated by 5-HT(1A/2C/1B) receptors and that blockade of any of its components produces a degradation of its discriminative effects.
Progressive ratio (PR) schedules had been widely used to study motivation to work for a reinforce... more Progressive ratio (PR) schedules had been widely used to study motivation to work for a reinforcer. After a post-reinforcer pause, subjects engage pressing a lever until a reinforcer is obtained. However, the discrete nature of lever presses allows alternative behaviors during inter-response time and had lead to the suggestion of several behavioral categories to explain pauses and work time. A progressive hold-down (PH) is incompatible with alternative responses and may allow a precise estimation of work time. Performance of rats trained in both PR and PH that received sucrose or intracranial self-stimulation (ICSS) as reinforcer were compared. We observed that rats mastered the PR and PH schedules. Post-reinforcer pauses, work time and inter-reinforcer time increased as a function of the response or hold requirement. However, rat’s performance suggest that the PH progression may be experienced by the rats as easier that the PR progression. Elimination of consummatory behavior with ...
Frontiers in Behavioral Neuroscience, 2022
Rats work very hard for intracranial self-stimulation (ICSS) and tradeoff effort or time allocati... more Rats work very hard for intracranial self-stimulation (ICSS) and tradeoff effort or time allocation for intensity and frequency parameters producing a sigmoidal function of the subjective reward magnitude of ICSS. Previous studies using electrical intracranial stimuli (ICS) as a discriminative cue focused on estimating detection thresholds or on the discrimination between intensities. To our knowledge, there is no direct comparison of the reinforcer tradeoff functions with the discriminative functions. Rats were trained to press and hold the lever for ICSS using the maximum reinforcing intensity below motor alterations or avoidance behavior. First, rats were trained to hold the lever for 1 s; after stability, they undergo trials where intensity or frequency was decreased on 0.1 log step. Thereafter, they undergo further training with a hold of 2 and later of 4 s to determine tradeoff with intensity or frequency. The same rats were trained on a discrimination task where the previousl...
Revista Mexicana de Análisis de la Conducta; Vol 7, No 2 (1981); 159-164, Sep 23, 2011
The performonce of an instrumental response, maintained under o fixed-interval schedule, was stud... more The performonce of an instrumental response, maintained under o fixed-interval schedule, was studied 30 sec., 40 min., 4 hr. and 8 hs.. afterr administering holoperidol, in rats. A marked reduction of operant responding was seen after the first two periods, and a behavioral recovery, of about 50% of control response rates, during the last two periods. A marked decrement in food and water intake was olso seen after the first three periods, and a near-normal intake 8 hr. after the treatment It is known that the administration of kaloperidol produces a specific and signiflcant reductton of acetylcitoline levels in tite caudate nucleus. Token togetiter, these data give fitrther support to the hypotitesis The performance of instrumental tasks is critically dependent upon the cholinergic activity of the caudate nucleus.
Revista Mexicana de Análisis de la Conducta; Vol 12, No 2 (1986): SEPTIEMBRE 1986; 157-167, May 23, 2011
En el presente trabajo se presenta una revision de los trabajos que analizan las propiedades diso... more En el presente trabajo se presenta una revision de los trabajos que analizan las propiedades disociativas del alcohol asi como de aquellos en los que se utiliza la administracion de este como estimulo discriminativo. Tambien se presenta un resumen de los resultados obtenidos cuando se realizan pruebas de generalizacion de estimulos con sujetos entrenados previamente a discriminar la administracion del alcohol de alguna otra condicion farmacologica. De los trabajos revisados se puede concluir que el alcohol posee efectos disociativos y que su administracion puede ser utilizada como senal discriminativa; sin embargo, estos efectos son singulares ya que la mayoria de las drogas evaluadas en las pruebas de generalizacion de estimulos no se generalizan con la senal discriminativa del alcohol. La excepcion la constituyen los barbituricos (aunque se ha demostrado que los sujetos pueden diferenciar entre la administracion del alcohol y los barbituricos) y el 3-carboxisalsolinol, que es un producto metabolico del alcohol. Finalmente, se han observado diferencias en el grado de disociacion dependiendo de si el entrenamiento inicial se realizo bajo los efectos del alcoholo de alguna otra condicion farmacologica
Proceedings of the Western Pharmacology Society
Proceedings of the Western Pharmacology Society, 1998
Proceedings of the Western Pharmacology Society, 1998
Revista Mexicana de Análisis de la Conducta, 2011
Journal of Neural Transplantation and Plasticity, 1992
Revista Mexicana de Análisis de la Conducta, 2011
... O'Dell, LE, Sussman, AN, Meyer, KL, Neisewander, JL Behavioral effects of psychomotor sti... more ... O'Dell, LE, Sussman, AN, Meyer, KL, Neisewander, JL Behavioral effects of psychomotor stimulant infusions into amygdaloid nuclei. Neuropsychopharmacology 1999.20(6): 591-602. Orozco, G, López-Cabrera, M., Velazquez-Martinez, DN Control de estímu-los con fármacos ...
Pharmacological reports : PR
Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the mesolimbic dopamine... more Drugs of abuse, such as amphetamine (AMPH), share the ability to activate the mesolimbic dopamine (DA) system. The behavioral effects of AMPH are largely mediated by increased DA neurotransmission in the nucleus accumbens. However, there is evidence that serotonin (5-hydroxytryptamine - 5-HT) systems may regulate forebrain DA function. We examined the role of 5-HT1B receptors on the discriminative stimulus properties of AMPH using conditioned taste aversion (CTA) as the drug discrimination procedure. Male Wistar rats were deprived of water and trained in the CTA procedure. They received the administration of AMPH (1.0 mg/kg) before a 10 min period of access to saccharin solution and followed by an injection of LiCl; on alternate days, rats received saline before and after the access to saccharin solution. In generalization and combination tests, the training dose of AMPH was substituted by 5-HT1B receptor ligands RU24969 (5-HT1B agonist: 0.1, 0.3 and 1.0 mg/kg), CP94253 (5-HT1B agon...
Psychopharmacology, 1996
Acute treatment with antidepressant drugs is known to increase the mean interresponse time (IRT) ... more Acute treatment with antidepressant drugs is known to increase the mean interresponse time (IRT) in the IRT>72-s schedule of reinforcement. In order to examine the possibility that this effect may reflect an action of the antidepressants on timing processes, we tested the effects of two antidepressants, desipramine and fluvoxamine, on behaviour maintained under two other timing schedules in rats. In the fixed-interval peak procedure (fixed-interval 30-s), acute treatment with desipramine (8mgkg-~) reduced response rate, whereas acute treatment with fluvoxamine (8 mg kg-a) increased it. Neither drug significantly altered the time to attainment of peak response rate or the Weber fraction. In the interval bisection task (standard durations 2 s and 8 s), the bisection point was not significantly altered by acute treatment with either drug. Chronic treatment with desipramine (8 mg kg-t b.d.) had no effect on any of the indices of timing under either schedule. Chronic treatment with fluvoxamine (8 mg kg-1 b.d.) reduced the time to attainment of peak response rate but had no effect on the Weber fraction under the fixed-interval peak procedure, and did not alter the bisection point or Weber fraction under the interval bisection procedure. The failure of desipramine and fluvoxamine to increase the time to peak response rate or the bisection point at doses that significantly altered operant response rate suggests that the effect of these drugs on IRT schedule performance is unlikely to reflect an interaction with timing processes.
Psychopharmacology, 2002
Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive beh... more Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size and delay) has been proposed as a model of "impulsive choice" in animals. Objective: A quantitative method was used to analyse inter-temporal choice in rats with lesions of the OPFC and sham-lesioned control rats. Methods: Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC (0.1 M, 0.5 l; two injections in each hemisphere), or sham lesions (injections of the vehicle). They were trained to press two levers (A and B) for sucrose reinforcement (0.6 M) in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of 50 l of the sucrose solution after a delay d A ; a press on B resulted in delivery of 100 l of the same solution after a delay d B. d B was increased progressively across successive blocks of six trials in each session, while d A was manipulated systematically across phases of the experiment. The indifference delay, d B(50) (value of d B corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of d B(50) versus d A were derived, and the parameters of the function compared between the groups. The locations of the lesions were verified histologically at the end of the experiment. Results: In both groups, d B(50) increased linearly with d A (r 2 >0.98 in each case). The slope of the function was significantly steeper in the lesioned group than the sham-lesioned group, whereas the intercept did not differ significantly between the groups. The brains of the lesioned rats showed extensive atrophy/gliosis of the OPFC, with sparing of the dorsolateral prefrontal cortex. Conclusions: The results indicate that lesions of the OPFC can alter inter-temporal choice, either promoting or suppressing "impulsive choice", depending upon the relative sizes and delays of the two choice alternatives. Theoretical analysis based on a quantitative model of inter-temporal choice indicates that the pattern of effect of the OPFC lesion is likely to reflect two actions: (i) an increase in the rate of time discounting; (ii) an increase in sensitivity to the ratio of the sizes of two reinforcers.
Psychopharmacology, 1995
This experiment examined the effect of destroying central noradrenergic neurones, using the selec... more This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) on the acquisition and performance of discrimination between two time intervals. Rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and lever B following an 8-s presentation of the same stimulus. Both groups acquired the discrimination (> 90% correct choices) within 15 sessions; however, the DSP4-treated group showed significantly slower acquisition than the control group. When stable performance had been attained, 'probe' trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. Neither the bisection point (duration corresponding to 50% choice of lever B) nor the Weber fraction differed significantly between the DSP4-treated and control groups. The levels of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the levels of dopamine and 5-hydroxytryptamine were not altered. The results indicate that noradrenaline depletion induced by DSP4 retarded the acquisition of temporal discrimination, but did not impair steady-state discriminative precision.
Psychopharmacology, 1996
This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTe... more This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule. Rats received either injections of 5,7dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for a sucrose reinforcer. Training sessions consisted of 40, 50-s trials in which reinforcers were available on a variable-interval 25-s schedule; in the first 25 s of each trial, reintbrcers were only available for responses on lever A, whereas in the last 25 s reinforcers were available only tbr responses on lever B. Data were collected from probe trials (/bur per session) in which no reinforcers were delivered, during the last ten of 50 training sessions. Both groups showed decreasing response rates on lever A and increasing response rates on lever B as a function of time from the onset of the trial. Response rate on lever B, expressed as a percentage of overall response rate, could be described by a two-parameter logistic function; neither the indifference point (i.e. the time corresponding to 50% responding on lever B) nor the slope of the function differed between the two groups. However, the lesioned group showed a higher rate of switching between response alternatives than the sham-lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results confirm previous findings that behaviour in timing
Psychopharmacology, 2004
Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive beh... more Rationale: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size and delay) has been proposed as a model of "impulsive choice" in animals. We recently found that destruction of the OPFC disrupted inter-temporal choice in rats. It is not known whether the dopaminergic projection to the OPFC contributes to the regulation of inter-temporal choice. Objective: A quantitative method was used to compare intertemporal choice in rats whose OPFC had been depleted of dopamine with that of sham-lesioned control rats. Methods: Under halothane anaesthesia, rats received injections of 6-hydroxydopamine into the OPFC (2 mg ml 1 , 0.5 ml, two injections in each hemisphere), or sham lesions (injections of the vehicle). They were trained to press two levers (A and B) for sucrose reinforcement (0.6 M) in discrete-trials schedules. In free-choice trials, a press on A resulted in delivery of 50 ml of the sucrose solution after a delay d A ; a press on B resulted in delivery of 100 ml of the same solution after a delay d B. d B was increased progressively across successive blocks of six trials in each session, while d A was manipulated systematically across phases of the experiment. The indifference delay, d B(50) (value of d B corresponding to 50% choice of B) was estimated for each rat in each phase. Linear functions of d B(50) versus d A were derived, and the parameters of the function compared between the groups. Concentrations of monoamines in the OPFC were determined by highperformance liquid chromatography at the end of the experiment. Results: In both groups, d B(50) increased linearly with d A (r 2 >0.9 in each case). The slope of the function was significantly steeper in the lesioned group than the sham-lesioned group, whereas the intercept did not differ significantly between the groups. When delays of 4 or 8 s were imposed on the smaller reinforcer, the lesioned rats showed greater tolerance of delay to the larger reinforcer (i.e. they exhibited longer values of d B(50)) than the sham-lesioned rats. Dopamine, noradrenaline and 5-hydroxytryptamine levels in the OPFC of the lesioned group were 20, 75 and 98% of those of the shamlesioned group. Conclusions: The results indicate that dopaminergic afferents to the OPFC contribute to the regulation of inter-temporal choice behaviour due to their role in determining organisms' sensitivity both to reinforcer size and to delay of reinforcement.
Pharmacology Biochemistry and Behavior, 2002
Interval timing behaviour is revealed by prospective, immediate and retrospective timing schedule... more Interval timing behaviour is revealed by prospective, immediate and retrospective timing schedules. Prospective timing tasks are used to study intertemporal choice (choice between outcomes occurring after different delays), immediate timing tasks to study temporal differentiation (temporal regulation of the animal's behaviour) and retrospective timing tasks to study temporal discrimination (discrimination between the durations of external events). Central 5-hydroxytryptamine (5-HT) depletion promotes preference for small early reinforcers over large delayed reinforcers, possibly by facilitating the time-dependent degradation of reinforcer value. Central 5-HT depletion retards the learning of temporal differentiation, and increases the variability of timing in some immediate timing tasks; however, it does not impede (in some cases it facilitates) the acquisition of temporal discrimination. Attempts to ascribe all the effects of 5-HT depletion on timing to a single behavioural process have been unsuccessful, although disinhibition of switching between operant responses may account for some of the findings. Acute treatment with drugs affecting 5-HTergic mechanisms alters timing behaviour in qualitatively different ways in different timing schedules, casting doubt on the idea that the effects of these drugs are mediated by interaction with a unitary timing process. The receptors that mediate 5-HT's putative involvement in interval timing behaviour remain to be identified.
Pharmacology Biochemistry and Behavior, 2003
Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine... more Indorenate (5-methoxytryptamine beta-methylcarboxylate, INDO) is a serotonin (5-hydroxytryptamine, 5-HT) agonist that has affinity for 5-HT(1A/1B/2C) receptors. Unlike other anxiolytics such as 5-HT receptor agonists, INDO may not share tolerance or dependency with the benzodiazepine anxiolytics. It has been reported that the discriminative stimulus properties of 5-HT(1A/1B/2C) agonists, but not those of 5-HT(3/4) agonists, generalize to INDO. Therefore, the aim of the present study was to obtain further evidence on the differential involvement of 5-HT(1A/1B/2C) receptors in the discriminative stimulus properties of INDO by evaluating its interactions with antagonists of the 5-HT(1A), 5-HT(1B), 5-HT(2C), and 5-HT(3/4) receptor subtypes. Rats were trained to discriminate INDO from saline in a conditioned taste aversion paradigm. For Group D(+)S(-), administration of INDO signalled that saccharin flavour was followed by LiCl, while injection of vehicle signalled safe consumption of saccharin solution. Group D(-)S(+) had the contingencies reversed. After this training, rats had generalization tests where INDO administration was preceded by different doses of the following antagonists: WAY100635 (5-HT(1A)), NAN190 (5-HT(1A)), methiothepin (5-HT(1A/1B/2C)), GR127935 (5-HT(1B/1D)), ketanserin (5-HT(2A/2C)), ritanserin (5-HT(2C/2A)), mesulergine (5-HT(2C/2A)), metergoline (5-HT(2C/2A)), SB206553 (5-HT(2B/2C)), and tropisetron (5-HT(3/4)). In Group D(+)S(-), the order of potency to block the discriminative stimulus properties of INDO was WAY100635>ketanserin>ritanserin>GR127935>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190, while in Group D(-)S(+), the order was WAY100635>GR127935>ketanserin>ritanserin>mesulergine congruent with SB206553>metergoline>methiothepin>NAN190. Tropisetron did not produce any alteration of the discriminative control by INDO. These results suggest that the discriminative signal of INDO is mediated by 5-HT(1A/2C/1B) receptors and that blockade of any of its components produces a degradation of its discriminative effects.