Segregation of Amphetamine Reward and Locomotor Stimulation between Nucleus Accumbens Medial Shell and Core (original) (raw)
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Brain Research, 1991
We investigated involvement of dopamine receptor subtypes and two dopaminergic terminal areas in the acquisition and the expression of the amphetamine conditioned place preference (CPP). When injected systemically before conditioning, both Dl and D2 dopamine antagonists blocked acquisition in a dose-dependent manner. When injected systemically before testing, the effects of the same Dl and D2 antagonists differed. The selective Dl antagonist SCH23390 dose-dependently blocked expression of the previously established conditioned behavior within the dose range that also blocked acquisition. In contrast, D2 antagonists failed to block expression of the amphetamine CPP at doses which blocked acquisition. Expression was, however, blocked by higher doses of D2 antagonists, which may have lost their selectivity for the D2 dopamine receptor. The expression of the CPP was also blocked by microinjections of SCH23390 or sulpiride into nucleus accumbens, but not into striatum. In a control experiment, sodium pentobarbital, which significantly reduced spontaneous locomotor activity in a manner similar to the higher doses of the dopamine antagonists, had no effect on the expression of the amphetamine CPP when given before testing. Finally, electrolytic lesions of the dorsal striatum potentiated the amphetamine CPP. These findings indicate that the dopamine released by amphetamine interacts with both Dl and D2 dopamine receptors to establish a CPP, but that the expression of the CPP may involve activation of the Dl dopamine receptor in the nucleus accumbens.
Psychopharmacology, 1993
The effects of local injections of dopamine receptor agonists into various areas within the nucleus accumbens or the medial caudate-putamen on the generation of lOcomotor activity were examined. Combinations of 0.32 gg/side of the dopamine receptor agonists SKF 38393 (D1) and quinpirole (D2) produced increases in locomotor activity that varied according to the rostral-caudal placement of the cannulae within the nucleus accumbens. The greatest levels of locomotion were generated by injections into a region in the caudal-central nucleus accumbens, with lower levels of activity elicited by injections into more rostral or caudal regions. A similar pattern of responses was produced by administration of the indirect dopamine agonist d-amphetamine. These results indicate that there is marked heterogeneity in the response of discrete sub-regions of the nucleus accumbens to dopamine receptor stimulation and that this heterogeneity is functionally expressed in the mediation of the locomotor effects of dopaminergic agonists.
2022
Amphetamine (AMPH) is a psychostimulant drug frequently related to addiction, which is characterized by functional and molecular changes in the brain reward system, favoring relapse development and pharmacotherapies have shown low effectiveness. Considering the beneficial influences of tactile stimulation (TS) in different diseases that affect the central nervous system (CNS), here we evaluated if TS applied in adult rats could prevent or minimize the AMPH-relapse behavior also accessing molecular neuroadaptations in the Nucleus accumbens (NAc). Following AMPH conditioning in the conditioned place preference (CPP) paradigm, male rats were submitted to TS (15-min session, 3 times a day, for 8 days) during the drug abstinence period, which were re-exposed to the drug in the CPP paradigm for additional 3 days for relapse observation and molecular assessment. Our findings showed that besides AMPH relapse; TS prevented the dopamine transporter (DAT), dopamine 1 receptor (D1R), tyrosine h...
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.
Psychopharmacology, 1988
Lesion studies employing 6-hydroxydopamine (6-OHDA) suggest that locomotor hyperactivity induced by certain stimulant drugs is dependent on dopaminergic neurotransmission in the nucleus accumbens (NACC). However, studies to date have not adequately controlled for the reported effects of 6-OHDA on baseline (non-drug) activity and on DA levels in other terminal regions. Slow bilateral infusions of 6-OHDA into the NACC, but not into olfactory tubercle (OT) or medial prefrontal cortex (mPFCx), reduced d-amphetamine (0.5 mg/kg SC) hyperactivity and resulted in a "supersensitive" (hyperactive) response to a low dose of apomorphine (0.1 mg/kg SC) in photocell cages. Direct observation revealed no behavioral changes in OT lesioned rats challenged with apomorphine which might correspond to a "denervation supersensitivity" syndrome. Assays of DA and 5-hydroxytryptamine (5-HT) in mPFCx, OT, NACC, and caudate-putamen revealed that 6-OHDA infusion into NACC caused substantial DA loss in NACC, OT and mPFCx, whereas infusion at mPFCx or OT sites depleted DA locally (>85% loss) with little or no remote change. Concentrations of 5-HT were little altered by 6-OHDA, except for a local depletion in mPFCx. The present results confirm the importance of nucleus accumbens DA in the expression of locomotor stimulation induced by apomorphine and d-amphetamine, and suggest that the mPFCx and OT do not make an important contribution.
Drug-induced place preference in rats with 5,7-dihydroxytryptamine lesions of the nucleus accumbens
Behavioural Brain Research, 1988
The conditioned place preference (CPP) paradigm was used to determine a role for serotonin in the nucleus accumbens in the mediation of the rewarding properties of o-amphetamine morphine and diazepam. The effect of these drugs on CPP was examined in controls and in animals with 5,7-dihydroxytryptamine lesions of the nucleus accumbans. The results from control animals confirmed that D-amphetamine (1.5 mg/kg, i.p.), morphine (2.0 mg/kg, i.p.) and diazepam ( 1.0 mg/kg, i.p.) produced place preference for a distinctive environment that had previously been paired with injections of the drug. In animals with 80~o reduction of 5-hydroxytryptamine content of the nucleus accumbens, D-amphetamine CPP was unchanged and morphine CPP was attenuated compared with controls. Diazepam CPP was not apparent in animals with the lesion. In separate experiments, characteristic behavioural effects of the drugs under study were examined in control and in animals with lesion. The results showed a tendency for increased amphetamine hyperlocomotion, enhanced morphine activity and analgesia and decreased diazepam anti-anxiety effect in animals with lesions. Thus, the 5,7-dihydroxytryptamine lesions of the nucleus aecumbens differently influenced the CPP induced by the drugs studied and, with the exception of diazepam, the various behavioural effects elicited by each drug. The findings suggest that serotonin-containing neurones of the nucleus accumbens are a component of the neural circuitry that mediates the rewarding properties of morphine, probably of diazepam, but not of D-amphetamine.
Neuroscience Letters, 1993
The present study examined the roles of the ventral pallidum area, one output system of the nucleus accumbens, in the acquisition and expression of the amphetamine conditioned place preference (CPP). Pre-conditioning NMDA lesions of the ventral pallidum area completely abolished the acquisition of the CPP. By contrast, post-conditioning NMDA lesions of the same area had no effect on the expression of the CPP. These results suggest that the ventral pallidum area mediates some process that involves the primary, but not conditioned rewarding effects of amphetamine.
Brain Research, 2001
Previous research has demonstrated an interaction between the effects of amphetamine and exposure to a novel environment on the activity of neurons in the nucleus accumbens. Given a model in which these accumbens efferents gate the excitability of basal forebrain cholinergic corticopetal neurons, the administration of intra-accumbens amphetamine was hypothesized to potentiate the increase in cortical acetylcholine produced by introduction to a novel environment. Dual probe microdialysis revealed no synergistic interactions between exposure to a novel environment and amphetamine on nucleus accumbens dopamine or cortical acetylcholine efflux. This finding indicates that exposure to a novel environment failed to recruit the telencephalic activation of the nucleus accumbens presumably necessary to reveal modulatory effects of accumbens dopaminergic transmission on cortical acetylcholine release.
Brain Research, 1985
Injections of amphetamine into the nucleus accumbens increased locomotor activity of rats. St,bsequent in ections of procaine into the midbrain, in the region of the pedunculopontinc nucleus, significantly reduced the amphetamine-induced locomotor activit~. Control experiments showed that procaine injections into the contralateral pedunculopontine nucleus had little or no effect, as well as ipsilateral injections dorsal and ventral to the pedunculopontine nucleus. These findings suggest that release of dopaminc trom amphetamine injections into the accumbens gives rise to ipsilateral descending influences on the region of the pedunculopontine nucleus, a major component of the mesenccphalic locomotor region. Descending influences from the nucleus accumbens to mcsencephalic locomotor region may serve as a link for limbic-motor integration in behavioral response initiation.
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.