Prelimbic cortex is a common brain area activated during cue-induced reinstatement of cocaine and heroin seeking in a polydrug self-administration rat model

被引:24
作者
Rubio, Francisco J. [1 ]
Quintana-Feliciano, Richard [1 ]
Warren, Brandon L. [1 ]
Li, Xuan [2 ]
Witonsky, Kailyn F. R. [2 ]
del Valle, Frank Soto [1 ]
Selvam, Pooja V. [1 ]
Caprioli, Daniele [2 ,3 ]
Venniro, Marco [2 ]
Bossert, Jennifer M. [2 ]
Shaham, Yavin [2 ]
Hope, Bruce T. [1 ]
机构
[1] NIDA, Neuronal Ensembles Addict Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA
[2] NIDA, Neurobiol Relapse Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH, Baltimore, MD USA
[3] Santa Lucia Fdn, IRCCS, Rome, Italy
关键词
drug self-administration; Fos; neuronal ensembles; opioids; polydrug; psychostimulants; CONTEXT-INDUCED RELAPSE; NUCLEUS-ACCUMBENS SHELL; NEURONAL ENSEMBLES; PREFRONTAL CORTEX; CENTRAL AMYGDALA; DRUG-SEEKING; DIFFERENTIAL INVOLVEMENT; GLUTAMATE RECEPTORS; VENTRAL SUBICULUM; SUCROSE-SEEKING;
D O I
10.1111/ejn.14203
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:165 / 178
页数:14
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