Role of Dorsomedial Striatum Neuronal Ensembles in Incubation of Methamphetamine Craving after Voluntary Abstinence

Abstract

We recently developed a rat model of incubation of methamphetamine craving after choice-based voluntary abstinence. Here, we studied the role of dorsolateral striatum (DLS) and dorsomedial striatum (DMS) in this incubation. We trained rats to selfadminister palatable food pellets (

The Anterior Insular Cortex→Central Amygdala Glutamatergic Pathway Is Critical to Relapse after Contingency Management

“…In this regard, we found that inhibition of CeA, AIV, and the AIV→CeA projections decreased active lever presses by ~40–60% but did not completely block drug seeking (i.e., similar active versus inactive lever responding during the relapse test), further supporting the notion that other brain areas and circuits contribute to relapse after voluntary abstinence. Indeed, as mentioned in the Introduction, we recently identified a role of dorsomedial striatum neuronal ensembles in this form of relapse (Caprioli et al, 2017). …”

“…The two levers and the distinct food- and drug-associated cues were located on opposite sides of the self-administration chambers. Next, during the voluntary abstinence period (14 days), we gave the rats a mutually exclusive choice between the palatable food and methamphetamine (20 trials/day, 10 min inter-trial-interval); during the choice trials, the rats can earn either the palatable food or intravenous methamphetamine but not both (a contingency management manipulation) (Caprioli et al, 2015a; Caprioli et al, 2017; Caprioli et al, 2015b; Venniro et al, 2017). On the next day, we tested the rats for relapse to methamphetamine seeking.…”

“…We performed RNA in situ hybridization (ISH) for Fos , Drd1 , and Drd2 mRNAs as described previously (Caprioli et al, 2017; Li et al, 2015a; Rubio et al, 2015; Warren et al, 2016). Sixty min after the beginning of the test session, we briefly anesthetized the rats with isoflurane and decapitated them.…”

“…Between tests, we expose the rats to daily mutually exclusive choice sessions between the drug and food (Cantin et al, 2010; Caprioli et al, 2015b; Lenoir et al, 2007). Under these ‘contingency management’ conditions, like human addicts, male and female rats choose to abstain from methamphetamine or heroin when an alternative non-drug reward is available, but relapse to drug seeking when the alternative reward is removed (Caprioli et al, 2015a; Caprioli et al, 2017; Venniro et al, 2017). In our initial mechanistic study, we used the Daun02 inactivation procedure (Koya et al, 2009a) and found that dorsomedial striatum neuronal ensembles (identified by the neuronal activity marker Fos (Cruz et al, 2013; Morgan and Curran, 1991)) play a role in relapse to methamphetamine seeking after voluntary abstinence (Caprioli et al, 2017).…”

Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior

“…Furthermore, ensembles in the ventral medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC) were shown to encode the context-induced operant responding for heroin during relapse and after extended abstinence, respectively (Bossert et al, 2011, Fanous et al, 2012). Additionally, ensembles in the dorsal striatum were linked to voluntary abstinence from methamphetamine taking (Caprioli et al, 2017), ensembles in the central amygdala to craving alcohol and nicotine during abstinence (Funk et al, 2016, de Guglielmo et al, 2016), and ventral mPFC ensembles were found to suppress ethanol seeking and drive or inhibit seeking of natural rewards depending on environmental contingencies (Pfarr et al, 2015, Suto et al, 2016, Warren et al, 2016). Importantly, all these studies report a very small number of activated neurons in a given brain region (e.g., <5%), indicating that highly specific addictive behaviors are regulated by small ensembles of neurons throughout the brain.…”