Conditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum

doi:10.1016/0006-8993(95)01222-2

Brain Research

Volume 707, Issue 1, 22 January 1996, Pages 64-74

https://doi.org/10.1016/0006-8993(95)01222-2 Get rights and content

Abstract

The ventral pallidum (VP) is often viewed as an output structure of the nucleus accumbens septi (NAS). However, VP, like NAS, receives a dopaminergic input from the ventral tegmental area. These experiments investigated some behavioral effects of microinjection into VP of drugs which enhance dopaminergic transmission. Injection of 25 μg dopamine or 5–10 μg amphetamine into VP produced hypermotility. In contrast, injection of 12.5–50 μg cocaine initially suppressed, then increased, activity. Injection of 100 μg cocaine only produced hypomotility in the 1-h period examined. The hypomotility following cocaine seemed to be a local anesthetic effect, because it was mimicked by 50–200 μg procaine. Procaine did not, however, produce subsequent hypermotility. Conditioned place preference (CPP) was produced by 10 μg amphetamine and 50 μg cocaine but not 100 μg procaine. We conclude that injection of cocaine into VP, unlike similar injections into NAS, produces CPP. These results support the idea of an involvement of dopamine in VP in reward and locomotor activation, independent of dopamine in NAS. The use of intracerebral injections of cocaine is complicated, however, by an apparent local anesthetic effect of the drug.

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Citation Excerpt :
This cocaine-induced dopamine transmission that is required for the acquisition of CPP likely occurs in ventral striatal and pallidal regions. Dopaminergic denervation of the medial NAc shell, olfactory tubercle, or VP, but not the NAc core, using local 6-hydroxydopamine (6-OHDA) microinjections was inversely correlated with cocaine CPP scores (Gong et al., 1997; Sellings et al., 2006) and infusions of cocaine into the VP were sufficient to condition a place preference (Gong et al., 1996). Finally, systemic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist MK801 10 min prior to or immediately following cocaine conditioning sessions inhibited the acquisition of cocaine CPP (Cervo and Samanin, 1995), possibly by acting in the NAc shell (Li et al., 2016) or in the hippocampus (McDonald et al., 2005) to disrupt cocaine-associated contextual memory consolidation.
Women are more sensitive to cocaine craving elicited by stimuli associated with relapse. Ovarian hormones modulate cocaine craving and may therefore function as risk factors or therapeutic agents for the development and treatment of cocaine use disorder, respectively. We review herein the neuropharmacological effects of the steroid hormones 17ß-estradiol, progesterone, and allopregnanolone, a progesterone metabolite, in relation to their effects on cocaine-induced locomotion, behavioural sensitization, conditioned place preference, and reinstatement of cocaine seeking. In general, the literature suggests that female rats are more sensitive to these cocaine-induced behaviours than males and that 17ß-estradiol facilitates the expression of these sex differences. Alternatively, in females, exogenous progesterone attenuates cocaine conditioned place preference, reinstatement, and possibly behavioural sensitization, either on its own or after conversion to allopregnanolone. These opposing effects of 17ß-estradiol and progesterone/allopregnanolone involve endocannabinoid, γ-aminobutyric acid, dopamine, and glutamate transmission in the medial prefrontal cortex and striatum. We conclude that 17ß-estradiol may be a risk factor for various components of cocaine use disorder in women, whereas progesterone and allopregnanolone may be potential treatment options.
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The ventral pallidum (VP) is central to the reinforcing effects across a variety of drugs and relapse to drug seeking. Emerging studies from animal models of reinstatement reveal a complex neurobiology of the VP that contributes to different aspects of relapse to drug seeking. This review builds on classical understanding of the VP as part of the final common pathway of relapse but also discusses the properties of the VP as an independent structure. These include VP neural anatomical subregions, cellular heterogeneity, circuitry, neurotransmitters and peptides. Collectively, this review provides a current understanding of the VP from molecular to circuit level architecture that contributes to both the appetitive and aversive symptoms of drug addiction. We show the complex neurobiology of the VP in drug seeking, emphasizing its critical role in addiction, and review strategic approaches that target the VP to reduce relapse rates.
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Drugs of abuse induce persistent remodeling of reward circuit function, a process thought to underlie the emergence of drug craving and relapse to drug use. However, how circuit-specific, drug-induced molecular and cellular plasticity can have distributed effects on the mesolimbic dopamine reward system to facilitate relapse to drug use is not fully elucidated. Here, we demonstrate that dopamine receptor D3 (DRD3)-dependent plasticity in the ventral pallidum (VP) drives potentiation of dopamine release in the nucleus accumbens during relapse to cocaine seeking after abstinence. We show that two distinct VP DRD3⁺ neuronal populations projecting to either the lateral habenula (LHb) or the ventral tegmental area (VTA) display different patterns of activity during drug seeking following abstinence from cocaine self-administration and that selective suppression of elevated activity or DRD3 signaling in the LHb-projecting population reduces drug seeking. Together, our results uncover how circuit-specific DRD3-mediated plasticity contributes to the process of drug relapse.
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In our present experiments, the role of D2 dopamine (DA) receptors of the ventral pallidum (VP) was investigated in one trial step-through inhibitory avoidance paradigm.
Animals were shocked 3 times in the conditioning trial, with 0.5 mA current for 1 s. Subsequently bilateral microinjection of the D2 DA receptor agonist quinpirole was administered into the VP in three doses (0.1 μg, 1.0 μg or 5.0 μg in 0.4 μl saline). We also applied the D2 DA receptor antagonist sulpiride (0.4 μg in 0.4 μl saline) alone or 15 min prior to the agonist treatment to elucidate whether the agonist effect was specific for the D2 DA receptors. Control animals received saline. In a supplementary experiment, it was also investigated whether application of the same conditioning method leads to the formation of short-term memory in the experimental animals.
In the experiment with the D2 DA receptor agonist, only the 0.1 μg quinpirole increased significantly the step-through latency during the test trials: retention was significant compared to the controls even 2 weeks after conditioning. The D2 DA receptor antagonist sulpiride pretreatment proved that the effect was due to the agonist induced activation of the D2 DA receptors of the VP. The supplementary experiment demonstrated that short-term memory is formed after conditioning in the experimental animals, supporting that the agonist enhanced memory consolidation in the first two experiments.
Our results show that the activation of the D2 DA receptors in the VP facilitates memory consolidation as well as memory-retention in inhibitory avoidance paradigm.
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The role of dopamine (DA) receptors in spatial memory consolidation has been demonstrated in numerous brain regions, among others in the nucleus accumbens which innervates the ventral pallidum (VP). The VP contains both D1 and D2 DA receptors. We have recently shown that the VP D1 DA receptor activation facilitates consolidation of spatial memory in Morris water maze test. In the present study, the role of VP D2 DA receptors was investigated in the same paradigm.
In the first experiment, the D2 DA receptor agonist quinpirole was administered into the VP of male Wistar rats in three doses (0.1, 1.0 or 5.0 μg, respectively in 0.4 μl physiological saline). In the second experiment, the D2 DA receptor antagonist sulpiride was applied to elucidate whether it can antagonise the effects of quinpirole. The antagonist (4.0 μg, dissolved in 0.4 μl physiological saline) was microinjected into the VP either by itself or prior to 1.0 μg agonist treatment. Control animals received saline in both experiments.
The two higher doses (1.0 and 5.0 μg) of the agonist accelerated memory consolidation relative to controls and increased the stability of the consolidated memory against extinction. Sulpiride pretreatment antagonised the effects of quinpirole. In addition, the antagonist microinjected into the VP immediately after the second conditioning trial impaired learning functions.
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Research reportConditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum

Abstract

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Rewarding effects of amphetamine and cocaine in the nucleus accumbens and block by alphaflupenthixol

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Blockade of enkephalinergic and GABAergic mediated locomotion in the nucleus accumbens by muscimol in the ventral pallidum

Jap. J. Pharmac.

Anatomical dissociation of amphetamine's rewarding and aversive effects: an intracranial microinjection study

Psychopharmacology

Research report
Conditioned place preference and locomotor activation produced by injection of psychostimulants into ventral pallidum