Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by D-amphetamine (original) (raw)
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Dissociation in Effects of Lesions of the Nucleus Accumbens Core and Shell on Appetitive Pavlovian A
1999
Dopamine release within the nucleus accumbens (NAcc) has been associated with both the rewarding and locomotorstimulant effects of abused drugs. The functions of the NAcc core and shell were investigated in mediating amphetaminepotentiated conditioned reinforcement and locomotion. Rats were initially trained to associate a neutral stimulus (Pavlovian CS) with food reinforcement (US). After excitotoxic lesions that selectively destroyed either the NAcc core or shell, animals underwent additional CS-US training sessions and then were tested for the acquisition of a new instrumental response that produced the CS acting as a conditioned reinforcer (CR). Animals were infused intra-NAcc with D-amphetamine (0, 1, 3, 10, or 20 g) before each session. Shell lesions affected neither Pavlovian nor instrumental conditioning but completely abolished the potentiative effect of intra-NAcc amphetamine on responding with CR. Core-lesioned animals were impaired dur-ing the Pavlovian retraining sessions but showed no deficit in the acquisition of responding with CR. However, the selectivity in stimulant-induced potentiation of the CR lever was reduced, as intra-NAcc amphetamine infusions dose-dependently increased responding on both the CR lever and a nonreinforced (control) lever. Shell lesions produced hypoactivity and attenuated amphetamine-induced activity. In contrast, core lesions resulted in hyperactivity and enhanced the locomotorstimulating effect of amphetamine. These results indicate a functional dissociation of subregions of the NAcc; the shell is a critical site for stimulant effects underlying the enhancement of responding with CR and locomotion after intra-NAcc injections of amphetamine, whereas the core is implicated in mechanisms underlying the expression of CS-US associations.
Neuroscience, 2005
The selectively bred Roman high-and low-avoidance rats differ in emotionality and responsiveness to the motor effects of acute and repeated psychostimulant administration. These lines also show drastic differences in the neurochemical responses of their mesolimbic dopamine systems to addictive drugs. The nucleus accumbens is critically involved in the locomotor activation produced by psychostimulants and in the augmentation of this effect observed upon repeated drug administration (i.e. behavioral sensitization), although there is not a general consensus as to whether the nucleus accumbens-core or the nucleus accumbens-shell is preferentially involved in such alterations. This study was designed to evaluate the effects of acute amphetamine (0.20 mg/kg, s.c.) on dopamine output in the nucleus accumbens-shell and nucleus accumbens-core of the Roman lines under basal conditions (i.e. naïve rats) and after the repeated administration of amphetamine (1 mg/kg, s.c.؋10 days) or saline. We show that (1) in naïve rats, amphetamine caused a larger increment in dopamine output in the nucleus accumbens-shell vs the nucleus accumbens-core only in the Roman high-avoidance line; (2) repeated amphetamine elicits behavioral sensitization in Roman high-avoidance, but not Roman low-avoidance, rats; (3) in sensitized Roman highavoidance rats, amphetamine provokes a larger increment in dopamine output in the nucleus accumbens-core, and an attenuated dopaminergic response in the nucleus accumbens-shell, as compared with Roman high-avoidance rats repeatedly treated with saline; and (4) such neurochemical changes are not observed in the mesoaccumbens dopaminergic system of the sensitization-resistant Roman lowavoidance line. We propose that (1) Roman high-avoidance and Roman low-avoidance rats differ in the vulnerability to develop psychostimulant sensitization, (2) the nucleus accumbens-core and nucleus accumbens-shell subserve distinct functional roles in this phenomenon, and (3) comparative studies in the Roman lines may provide insight into the influence of neural substrates and genetic background on the individual vulnerability to addiction.
Behavioral neuroscience, 2014
The prediction-error model of dopamine (DA) signaling has largely been confirmed with various appetitive Pavlovian conditioning procedures and has been supported in tests of Pavlovian extinction. Studies have repeatedly shown, however, that extinction does not erase the original memory of conditioning as the prediction-error model presumes, putting the model at odds with contemporary views that treat extinction as an episode of learning rather than unlearning of conditioning. Here, we combined fast-scan cyclic voltammetry (FSCV) with appetitive Pavlovian conditioning to assess DA release directly during extinction and reinstatement. DA was monitored in the nucleus accumbens core, which plays a key role in reward processing. Following at least 4 daily sessions of 16 tone-food pairings, fast-scan cyclic voltammetry was performed while rats received additional tone-food pairings followed by tone alone presentations (i.e., extinction). Acquisition memory was reinstated with noncontingen...
Evidence for opiate-dopamine cross-sensitization in nucleus accumbens: Studies of conditioned reward
Brain Research Bulletin, 1992
Evidence for opiate-dopamine cross-sensitization in nucleus accumbens: Studies ofcondifioned reward. BRAIN RES BULL. 29(5), 675-680, 1992.-We investigated opiate-amphetamine interactions within the nucleus accumbens in responding for conditioned reward. Separate groups of animals received 4-day intra-accumbens treatment with either saline, morphine (0.5 &0.5 r.d), [D-Ala2 NMe-Phe4 Gly-olS]-Enkephalin (DAMGO; I.0 &0.5 PI), or [D-Pen2,5]-Enkephalin (DPEN; 2.0 pg/O.5 ~1). On two subsequent test days, these rats were given a challenge of d-amphetamine (2.0 and 10.0 pg/O.5 ~1) and responding for conditioned reward was measured. In the conditioned reinforcement (CR) procedure, fooddeprived animals were trained in an initial phase to associate a food reward (primary reinforcement) with a compound stimulus (light/click). In the next phase, a lever was introduced and responding on the lever produced the compound stimulus alone (secondary reinforcement). Previous evidence shows that psychostimulants but not opiates markedly potentiate responding for conditioned reward. In the present design, animals previously treated with either morphine or DAMGO (preferential mu agonists) showed potentiated lever responding following amphetamine challenges, relative to either DPEN-or saline-treated animals. These findings show that prior exposure of nucleus accumbens neurons to /l-selective opiates induces sensitization to the effects of amphetamine. The results are discussed in terms of opioid effects on dopamine transmission and second messenger systems. Opioids Receptor subtypes Dopamine Cross-sensitization Conditioned reinforcement
Behavioural Brain Research, 1993
The experiments reported here have investigated the impact on re,,vard-rclated processes of Icsioning the basolateral amsgdala, ventral subiculum and pretimbic cortex which represent the major limhic sources of ",ffl'erents to the ventral striatum. The results showed that. while lesions of the prelimbic cortex were without effect on the approach to a CS predictive of sucrose reinforcement and the acquisition of a new response with conditioned reinforcement, lesions of the other two structures significantly impaired both responses. Howe,,er. there '.~ere important dil-I'erences between the eft'cots of basolateral amygdala and ventral subiculum lesions. Thus, lesions of the ventral subiculum completel.,, abolished the loconlotor response to inlra-accumbens infusions of D-amphetamine, in addition to blocking the potentiative eftcot ot the same treatment em responding with conditioned reinforcement, l.esions of the basolateral am vgdala, b.v contrast, reduced the control over behaviour by a conditioned reinforcer, bt, t not the potentiation of that control by intra-accumbens D-amphetamine except at the highest dose. Moreover, the locomotor response to D-amphetamine-induced increases in dopamine in the nucleus accumbens was unaffected b,, amygdala lesions over the dose range blocked b5 ventral subiculum lesions. The results suggest a rather selective effect of am,,gdala-ventral striatal interactions ~n processes subserving conditioned reinforcement and a more fundamental influence of ventral st, biculum-venlral striatal interactions in mediating the psychomotor stimulant effects ol" D-amphetamine.
The Journal of Neuroscience, 2003
Convergent evidence suggests that amphetamine (AMPH) exerts its rewarding and locomotor stimulating effects via release of dopamine in the nucleus accumbens. However, there is no consensus as to the relative contributions of core and medial shell subregions to these effects. Moreover, the literature is based primarily on intracranial administration, which cannot fully mimic the drug distribution achieved by systemic administration. In the present study, the effects of bilateral 6-hydroxydopamine lesions of the accumbens core or medial shell on rewarding and locomotor stimulating effects of systemically administered amphetamine (0.75 mg/kg, i.p.) were examined in a conditioned place preference (CPP) procedure relying solely on tactile cues (floor texture). Residual dopamine innervation was quantified by [125I]-RTI-55 binding to the dopamine transporter. When lesions were performed before the conditioning phase, AMPH-induced locomotor stimulation and CPP magnitude were positively corr...
Neuropsychopharmacology, 2005
The abuse of substituted amphetamines such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA/ Ecstasy) can result in neurotoxicity, manifested as the depletion of dopamine (DA) and 5-hydroxytriptamine (5-HT; serotonin) axon terminal markers in humans and animal models. Human METH and MDMA users exhibit impairments in memory and executive functions, which may be a direct consequence of the neurotoxic potential of amphetamines. The objective of this study was to investigate the influence of amphetamines-induced neurotoxicity on Pavlovian learning. Using mouse models of selective DA neurotoxicity (METH; 5 mg/kg  3), selective 5-HT neurotoxicity (fenfluramine /FEN; 25 mg/kg  4) and dual DA and 5-HT neurotoxicity (MDMA; 15 mg/ kg  4), appetitive and aversive conditioning were investigated. Dopaminergic neurotoxicity significantly impaired METH and cocaine conditioned place preference (CPP), but had no effect on LiCl-induced conditioned place aversion (CPA). In contrast, serotonergic neurotoxicity significantly enhanced CPP, and had no effect on CPA. Dual dopaminergic/serotonergic neurotoxicity had no apparent effect on CPP; however, CPA was significantly attenuated. Postmortem analysis revealed that significantly diminished levels of DA and 5-HT markers persisted in the striatum, frontal cortex, hippocampus, and amygdala. These findings suggest that amphetamines-induced dopaminergic and serotonergic neurotoxicity exert opposing influences on the affective state produced by subsequent drug reward, while dual dopaminergic/serotonergic neurotoxicity impairs associative learning of aversive conditioning. Furthermore, results revealed that amphetamines-induced DA and 5-HT neurotoxicity modulates appetitive Pavlovian conditioning similar to other DA and 5-HT neurotoxins. Modulation of Pavlovian conditioning by amphetamines-induced neurotoxicity may be relevant to compulsive drug-seeking behavior in METH and MDMA abusers.
Frontiers in Integrative Neuroscience, 2010
The nucleus accumbens (NA) has been hypothesized to be part of a circuit in which cue-evoked information about expected outcomes is mobilized to guide behavior. Here we tested this hypothesis using a Pavlovian reinforcer devaluation task, previously applied to assess outcomeguided behavior after damage to regions such as the orbitofrontal cortex and amygdala that send projections to NA. Rats with sham lesions or neurotoxic lesions of either the core or shell subdivision of NA were trained to associate a 10-s CS+ with delivery of three food pellets. After training, half of the rats in each lesion group received food paired with illness induced by LiCl injections; the remaining rats received food and illness unpaired. Subsequently, responding to the CS+ was assessed in an extinction probe test. Both sham and lesioned rats conditioned to the CS+ and formed a conditioned taste aversion. However only sham rats reduced their conditioned responding as a result of reinforcer devaluation; devalued rats with lesions of either core or shell showed levels of responding that were similar to lesioned, non-devalued rats. This impairment was not due to the loss of motivational salience conferred to the CS+ in lesioned rats as both groups responded similarly for the cue in conditioned reinforcement testing. These data suggest that NA core and shell are part of a circuit necessary for the use of cue-evoked information about expected outcomes to guide behavior.
The role of dopamine in the accumbens core in the expression of Pavlovian-conditioned responses
European Journal of Neuroscience
The role of dopamine in reward is a topic of debate. For example, some have argued that phasic dopamine signaling provides a prediction-error signal necessary for stimulus-reward learning, whereas others have hypothesized that dopamine is not necessary for learning per se, but for attributing incentive motivational value (“incentive salience”) to reward cues. These psychological processes are difficult to tease apart, because they tend to change together. To disentangle them we took advantage of natural individual variation in the extent to which reward cues are attributed with incentive salience, and asked whether dopamine (specifically in the core of the nucleus accumbens) is necessary for the expression of two forms of Pavlovian conditioned approach behavior - one in which the cue acquires powerful motivational properties (sign-tracking) and another closely related one in which it does not (goal-tracking). After acquisition of these conditioned responses (CRs), intra-accumbens injection of the dopamine receptor antagonist flupenthixol markedly impaired the expression of a sign-tracking CR, but not a goal-tracking CR. Furthermore, dopamine antagonism did not produce a gradual extinction-like decline in behavior, but maximally impaired expression of a sign-tracking CR on the very first trial, indicating the effect was not due to new learning (i.e., it occurred in the absence of new prediction-error computations). The data support the view that dopamine in the accumbens core is not necessary for learning stimulus-reward associations, but in attributing incentive salience to reward cues, transforming predictive CSs into incentive stimuli with powerful motivational properties.