Comparison of the effects of buspirone and chlordiazepoxide on differential reinforcement of low rates of response (original) (raw)
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Comparison of the effects of buspirone and chlordiazepoxide on successive discrimination
Pharmacology Biochemistry and Behavior, 1991
Comparison of the effects of buspirone and chlordiazepoxide on successive discrimination. PHARMACOL BIOCHEM BEHAV 39(2) 275-278, 1991.--Buspirone is a novel anxiolytic which does not share the muscle relaxant, anticonvulsant and sedative properties of classical anxiolytics such as the benzodiazepines. It has variable effects in conflict tasks based on shock which normally show consistent effects with classical anxiolytics. The present experiment investigated the effects of buspirone on successive discrimination, a conflict task employing omission of reward rather than shock. Buspirone (3.3, 1.1 and 0.3 mg/kg, IP) and chlordiazepoxide (5 and 20 mg/kg, IP) were administered to separate groups of rats throughout acquisition of a visual successive discrimination. Chlordiazepoxide released nonrewarded responding in a dose-related fashion. The effects of buspirone were qualitatively similar in releasing response suppression but were both less in magnitude and less clearly related to dose. The experiment shows that the action of buspirone in successive discrimination tasks does not depend on the use of shock but, rather, appears to be a genuine failure to fully release behavioural inhibition.
Behavioral effects of acute and chronic buspirone
European Journal of Pharmacology, 1988
The effects of buspirone were studied in squirrel monkeys trained to lever-press under a fixed-interval schedule involving suppressed responding. Buspirone (0.01-0.1 mg/kg) generally did not increase rates of suppressed responding. Buspirone (0.01-0.1 mg/kg) generally did not increase rates of suppresed responding; 0.3 mg/kg of buspirone decreased rate. In comparison, diazepam (0.1-1.0 mg/kg) and CL 218872 (0.3-3.0 mg/kg) increased responding. Additionally, the effects of buspirone (0.01-0.3 mg/kg) were unchanged over a 12-day period of daily administration. The results show that buspirone has effects on schedule-controlled behavior of squirrel monkeys that differ from those of typical anxiolytic drugs.
Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans
Journal of Psychopharmacology, 1999
The e¡ects of buspirone, £uvoxamine and diazepam were investigated, using healthy volunteers, in an aversive conditioning paradigm, a putative model for conditioned anxiety. The main prediction was that buspirone, an anxiolytic agent which reduces activity in serotonin (5-hydroxytryptophan, 5-HT) neurones, would attenuate aversively conditioned skin conductance responses. Skin conductance responses were recorded to 10 neutral tones (habituation phase). Tone 11 was immediately followed by a 1-s 90-dB aversive white noise (unconditioned stimulus).The conditioning trial reinstated responding to a second presentation of the tones (extinction phase). Skin conductance response amplitude, inter-response level and spontaneous £uctuations were recorded. There were ¢ve treatment groups comprising ¢ve men and ¢ve women. One control group took placebo, another control group received nothing; there was no e¡ect of placebo on any measure. Diazepam (2 mg, p.o.), a positive comparator, markedly reduced the amplitude of skin conductance responses at all phases of the experiment, but only in women. Buspirone (5 mg, p.o.) had the predicted e¡ect of accelerating extinction but also of unexpectedly accelerated habituation of skin conductance responses. There was a trend to reduce spontaneous £uctuations and no e¡ect on skin conductance level. The e¡ects of buspirone were thus speci¢c to responses to stimuli. Fluvoxamine (25 mg, p.o.) had similar e¡ects to buspirone and diazepam in women. An action common to buspirone, £uvoxamine and diazepam, which may account for their shared e¡ect on conditioned autonomic responses, is the suppression of neural activity in the dorsal raphe nucleus. It is argued that enhanced habituation must involve a di¡erent mechanism, such as enhanced 5-HT 1A function in the terminal ¢elds of the median raphe nucleus.
Psychopharmacology, 1993
A procedure was developed with pigeons to extend the experimental analysis of punished behavior and the effects of anxiolytic drugs. Under this procedure the completion of a fixed-ratio requirement on a changeover key switched between two variable-interval schedtries of reinforcement that were programmed on a second response key. Under one schedule, correlated with a green keylight, key pecks produced only food; under the second schedule, correlated with a red keylight, key pecks produced both food and electric shock. Pigeons were switched into the component with shock if they did not enter that component within 5 rain. Parameter values of the variable-interval schedules were manipulated systematically and the effects of two clinically active anxiolytic drugs, buspirone and chlordiazepoxide, were examined. Responding was suppressed during the component with shock (punishment) and, under non-drug conditions, pigeons infrequently switched into the punishment component; changeover responses occurred rapidly when switched into the punishment component. Both buspirone (0.1-3.0 mg/kg) and chlordiazepoxide (3.0-30 mg/ kg) increased punished responding at doses that had little effect on unpunished responding; d-amphetamine (0.3-5.6 mg/kg), which was studied only under one parameter of the variable-interval schedule, produced greater decreases in rates of punished responding than in unpunished responding. Changeover responses were increased only moderately by the anxiolytic drugs when the punishment schedule was added to a 3-rain variable-interval schedule and the alternate schedule was a 1-min variableinterval schedule without punishment; the amount of time spent in the punishment component, however, increased twofold at the higher doses of chlordiazepoxide. When these conditions were reversed and punishment
Buspirone effects in an animal conflict procedure: Comparison with diazepam and phenobarbital
Pharmacology Biochemistry and Behavior, 1987
been introduced as a novel non-benzodiazepine anti-anxiety agent. The Conditioned Suppression of Drinking (CSD) paradigm is an "animal model" for anxiety which provides information on both the relative potency and relative efficacy of anti-conflict agents. The present study compared the anti-conflict effects of buspirone to those of more "classical" anti-anxiety agents, diazepam and phenobarbital. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA), electrification being signalled by a tone. Within 2-3 weeks control CSD responding had stabilized (approximately 15-20 shocks/session and 10-15 ml water/session); drug tests were conducted at weekly intervals. Diazepam and phenobarbital markedly (400-500%) increased the number of shocks received at doses which did not depress background responding (i.e., water intake). A number of agents, most notably morphine and ethanol, did not reliably affect punished responding in the CSD. Administered IP, low doses (0.25-1 mg/kg) of buspirone increased punished responding only slightly (less than 100% increase); higher doses (2, 4 mg/kg) depressed background responding. Administered SC, buspirone (0.125-1.0 mg/kg) had more potent effects on both punished and unpunished responding; again, anti-conflict efficacy was only marginal. These results suggest that buspirone might be less effective than the benzodiazepines in the management of anxiety.
Buspirone And Anxiety Disorders: A Review With Pharmacological And Clinical Perspectives
The Internet Journal of Pharmacology, 2008
The treatment of anxiety is one of the leading problems in medicine today. Buspirone, an azpirone derivative and a 5-HT-1A (5hydroxytryptamine-1A) partial agonist, is the first nonbenzodiazepine anxiolytic introduced into medicine for the treatment of generalized anxiety disorder (GAD). It has a strong affinity for the 5-HT-1A receptor and does not appear to interact at the benzodiazepine receptor complex. Buspirone's distinctive mechanism of action helps to avoid pharmacological properties ancillary to the treatment of anxiety and contributes towards an apparently superior safety profile with generally fewer and more tolerable adverse effects than benzodiazepines. This article provides a brief overview on the results of animals and clinical studies in which the potential for buspirone dependence or abuse and the effects of its withdrawal were assessed. The pharmacology of serotonin systems and its role in the management of anxiety, along with the review of the contemporary literature is also discussed.
Psychopharmacology, 1994
The effects of four serotonin (5-HT)-IA compounds (buspirone, gepirone, ipsapirone and zalospirone) were compared with 5-hydroxytryptophan (5-HTP) [a 5-HT precursor with antidepressant (AD) efficacy], and diazepam (a benzodiazepine anxiolytic), on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Past research has shown that AD and anxiolytic compounds each have distinct effects on the DRL 72-s interresponse time (IRT) distribution profile. In the present paper, the profile of the IRT distribution was quantitatively characterized by three metrics: burst ratio, peak location and peak area. 5-HTP shifted the IRT distribution peak toward longer IRT durations, increased reinforcement rate and decreased response rate. The profile of the IRT distribution was not disrupted by 5-HTP. Diazepam disrupted the IRT distribution and increased bursting. In general, the arylpiperazine, 5-HT1A compounds increased reinforcement rate, decreased response rate and disrupted the profile of the IRT distribution. The effects of the four arylpiperazine 5-HT1A compounds on the IRT distribution profile were different from the AD profile of 5-HTP and the benzodiazepine anxiolytic profile of diazepam. Disruption of the IRT distribution by buspirone, gepirone, ipsapirone and zalospirone may result from decreased 5-HT transmission mediated by the presynaptic, somatodendritic 5-HT1A receptor.
Psychopharmacological Profile of Buspirone: A Critical Overview
benzodiazepine anxiolytics in that it does not interact with the benzodiazepine-gamma aminobutyric acid (GABA) chloride channel ionophore complex or facilitate the action of GABA at GABAA receptors and its behavioural effects are not blocked by benzodiazepine antagonists Further, buspirone is relatively nonsedating, is not a muscle relaxant or an anticonvulsant, and does not interact with alcohol. It also does not appear to cause tolerance or withdrawal reactions and does not show cross-tolerance with benzodiazepines or other sedatives. Buspirone has beneficial actions in anxious patients particularly those with generalized anxiety of mild or moderate severity. Unlike potent benzodiazepines, buspirone lacks beneficial actions in severe anxiety with panic attacks. In this brief critical overview, we consider the biochemical and behavioural pharmacology of anxiolytic buspirone.
Behavioral and neurochemical studies on the anticonflict actions of buspirone
Drug Development Research, 1984
A series of behavioral and neurochemical studies were performed in order to determine if buspirone (or an active metabolite of this compound) could perturb a component of the 7aminobutyric (GABA)-benzodiazepine receptor-chloride ionophore complex. In confirmation of previous findings, buspirone was shown to have anticonflict actions in both the rat and monkey. However, in these tests, buspirone was not as efficacious as benzodiazepines in producing an anticonflict action. The benzodiazepine receptor antagonists CGS 8216 and Ro 15-1788 did not reverse the anticonflict actions of buspirone. Small but statistically significant increases in the binding of [3H]diazepam to brain were observed in vivo after doses of buspirone which are active in the "thirsty rat conflict" test. However, a similar change was not observed in the ex vivo binding of [3H]flunitrazepam. These observations suggest that a metabolite of buspirone may perturb some component of the GABAbenzodiazepine receptor-chloride ionophore complex in an indirect fashion. Further work is necessary to determine whether a causal relationship exists between the changes in [3H]diazepam binding observed in vivo and the anticonflict actions of buspirone.