Ventral pallidum cellular and pathway specificity in drug seeking

2021 ◽  
Author(s):  
Yonatan Kupchik ◽  
Asheeta A. Prasad
Keyword(s):  
Ventral Pallidum ◽  
Drug Seeking

scholarly journals Ventral Pallidum is Essential for Cocaine Reinstatement After Voluntary Abstinence

2019 ◽  
Author(s):  
Mitchell R. Farrell ◽  
Christina M. Ruiz ◽  
Erik Castillo ◽  
Lauren Faget ◽  
Christine Khanbijian ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Neural Activity ◽  
Neural Circuits ◽  
Brain Regions ◽  
Extinction Training ◽  
Therapeutic Interventions ◽  
Ventral Pallidum ◽  
Approach And Avoidance ◽  
Drug Seeking ◽  
Cocaine Seeking

AbstractAddiction is a chronic relapsing disorder, and during recovery many people experience several relapse events as they attempt to voluntarily abstain from drug. New preclinical relapse models have emerged which capture this common human experience of relapse after voluntary abstinence, and mounting evidence indicates that reinstatement of drug seeking after voluntary abstinence recruits neural circuits distinct from reinstatement following experimenter-imposed abstinence, or abstinence due to extinction training. Ventral pallidum (VP), a key limbic node involved in drug seeking, has well-established roles in conventional reinstatement models tested following extinction training, but it is unclear whether this region also participates in more translationally-relevant models of relapse. Here we show that chemogenetic inhibition of VP neurons strongly attenuates cocaine-, context-, and cue-induced reinstatement tested after voluntary, punishment-induced abstinence. This effect was strongest in the most compulsive, punishment-resistant rats, and reinstatement was associated with neural activity in anatomically-defined VP subregions. VP inhibition also attenuated the propensity of rats to display ‘hesitations,’ a risk assessment behavior seen during punished drug taking that is likely due to concurrent approach and avoidance motivations. These results indicate that VP, unlike other connected limbic brain regions, is essential for reinstatement of drug seeking after voluntary abstinence. Since VP inhibition effects were strongest in the most compulsively cocaine-seeking individuals, this could indicate that VP plays a particularly important role in the most pathological, addiction-like behavior, making it an attractive target for future therapeutic interventions.

scholarly journals Astrocytes in the ventral pallidum extinguish heroin seeking through GAT-3 upregulation and morphological plasticity at D1-MSN terminals

2021 ◽  
Author(s):  
Anna Kruyer ◽  
Danielle Dixon ◽  
Ariana Angelis ◽  
Davide Amato ◽  
Peter W. Kalivas
Keyword(s):  
Morphological Plasticity ◽  
Female Rats ◽  
Ventral Pallidum ◽  
Actin Binding ◽  
Gaba Uptake ◽  
Opioid Use ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Drug Seeking ◽  
Male And Female Rats

AbstractGABAergic projections from the nucleus accumbens core to the dorsolateral ventral pallidum are necessary for drug-conditioned cues to initiate relapse-like drug seeking. Astrocytes in the ventral pallidum are situated perisynaptically and regulate GABA transmission through expression of GABA uptake transporters, but whether they are involved in regulating drug seeking is unknown. To determine the contribution of ventral pallidal astrocytes to heroin seeking, we labeled astrocytes in male and female rats with a membrane-bound fluorescent tag and used confocal microscopy to quantify astroglial expression of the GABA transporter GAT-3 and astrocyte synaptic proximity after withdrawal from heroin self-administration and during 15 min of cued heroin seeking. We found that GAT-3 was upregulated in rats that had extinguished heroin seeking, but not in animals that were withdrawn from heroin without extinction training or in rats that extinguished sucrose seeking. When GAT-3 upregulation was reversed using a vivo-morpholino oligo, heroin seeking was restored in the extinguished context and extinction of cued heroin seeking was disrupted compared to control animals. Although astrocyte synaptic proximity was not altered overall after heroin withdrawal, examination of astrocyte proximity to accumbens D1- or D2-expressing afferents revealed a selective increase in astrocyte proximity with D1-expressing terminals during extinction of heroin self-administration. Experimentally-induced reduction of astrocyte synaptic proximity through knockdown of the astrocyte-selective actin-binding protein ezrin also markedly disrupted extinction of heroin seeking. Notably, GAT-3 or ezrin knockdown had no impact on context- or cue-induced seeking in sucrose-trained animals. These data show that astrocytes in the ventral pallidum undergo plasticity after extinction of heroin use that reduces seeking and highlight the importance of astrocyte-neuron interactions in shaping behaviors associated with opioid use disorder.

The Grasp Cell Hypothesis: Near-miss effect points to common neurological machinery in posterior parietal cortex for controllable objects and concepts

2018 ◽  
Author(s):  
Imogen M Kruse
Keyword(s):  
Parietal Cortex ◽  
Posterior Parietal Cortex ◽  
Near Miss ◽  
Illusion Of Control ◽  
Gambling Behaviour ◽  
Drug Seeking ◽  
Spatial Influence ◽  
Reward Probability ◽  
Posterior Parietal ◽  
Action Value

The near-miss effect in gambling behaviour occurs when an outcome which is close to a win outcome invigorates gambling behaviour notwithstanding lack of associated reward. In this paper I postulate that the processing of concepts which are deemed controllable is rooted in neurological machinery located in the posterior parietal cortex specialised for the processing of objects which are immediately actionable or controllable because they are within reach. I theorise that the use of a common machinery facilitates spatial influence on the perception of concepts such that the win outcome which is 'almost complete' is perceived as being 'almost within reach'. The perceived realisability of the win increases subjective reward probability and the associated expected action value which impacts decision-making and behaviour. This novel hypothesis is the first to offer a neurological model which can comprehensively explain many empirical findings associated with the near-miss effect as well as other gambling phenomena such as the ‘illusion of control’. Furthermore, when extended to other compulsive behaviours such as drug addiction, the model can offer an explanation for continued drug-seeking following devaluation and for the increase in cravings in response to perceived opportunity to self-administer, neither of which can be explained by simple reinforcement models alone. This paper therefore provides an innovative and unifying perspective for the study and treatment of behavioural and substance addictions.

Sign in / Sign up

Export Citation Format

Share Document