Prelimbic cortex is a common brain area activated during cue‐induced reinstatement of cocaine and heroin seeking in a polydrug self‐administration rat model. (9th November 2018)

• Record Type: Journal Article
• Authors: Rubio, Francisco J.; Quintana‐Feliciano, Richard; Warren, Brandon L.; Li, Xuan; Witonsky, Kailyn F. R.; Valle, Frank Soto del; Selvam, Pooja V.; Caprioli, Daniele; Venniro, Marco; Bossert, Jennifer M.; Shaham, Yavin; Hope, Bruce T.
• Is Part Of: European journal of neuroscience. Volume 49:Number 2(2019)
• Page Start: 165
• Page End: 178
• Publication Date: 2018-11-09
• Subjects: drug self‐administration -- Fos -- neuronal ensembles -- opioids -- polydrug -- psychostimulants; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.14203
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Many preclinical studies examined cue‐induced relapse to heroin and cocaine seeking in animal models, but most of these studies examined only one drug at a time. In human addicts, however, polydrug use of cocaine and heroin is common. We used a polydrug self‐administration relapse model in rats to determine similarities and differences in brain areas activated during cue‐induced reinstatement of heroin and cocaine seeking. We trained rats to lever press for cocaine (1.0 mg/kg per infusion, 3‐hr/day, 18 day) or heroin (0.03 mg/kg per infusion) on alternating days (9 day for each drug); drug infusions were paired with either intermittent or continuous light cue. Next, the rats underwent extinction training followed by tests for cue‐induced reinstatement where they were exposed to either heroin‐ or cocaine‐associated cues. We observed cue‐selective reinstatement of drug seeking: the heroin cue selectively reinstated heroin seeking and the cocaine cue selectively reinstated cocaine seeking. We used Fos immunohistochemistry to assess cue‐induced neuronal activation in different subregions of the medial prefrontal cortex, dorsal striatum, nucleus accumbens, and amygdala. Fos expression results indicated that only the prelimbic cortex (PL) was activated by both heroin and cocaine cues; in contrast, no significant cue‐induced neuronal activation was observed in other brain areas. RNA in situ hybridization indicated that the proportion of glutamatergic and GABAergic markers in PL Fos‐expressing cells was similar for the heroin and cocaine cue‐activated neurons. Overall, the results indicate that PL may be a common brain area involved in both heroin and cocaine seeking during polydrug use. Abstract : We used a polydrug self‐administration model to study heroin and cocaine cue‐induced reinstatement and observed drug cue‐selective responding. Re‐exposure to the cocaine cue or heroin cue induced Fos expression in a mixed population of glutamatergic and GABAergic neurons specifically in the PL area, with no differences in other brain areas investigated. Activation of PL may be a common substrate for cocaine and heroin cue‐induced relapse in polydrug users.