Sensitization of neuronal response to cocaine during withdrawal following chronic treatment.
The neural basis of sensitization was examined by assessing the expression of zif/268 mRNA in cortical and striatal neurons following cocaine challenge (30 mg kg-1, i.p.) after 2 weeks of daily treatment with cocaine or saline vehicle. Acute cocaine challenge induced zif/268 mRNA expression in neurons of the caudate putamen (CP), nucleus accumbens (NAc) shell and prelimbic cortex. Chronic cocaine treatment attenuated zif/268 mRNA expression in these regions, although zif/268 mRNA response in CP neurons recovered after 7 days of withdrawal. In contrast, cocaine challenge during withdrawal augmented zif/268 response in neurons of the infralimbic cortex and olfactory tubercle. Sensitized activity in these regions could serve to amplify mesolimbic dopamine and NAc responses, and might provide a critical stimulus to drug craving.
Department of Psychiatry, Boston, MA 02111, USA.
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RP
Hammer
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ES
Cooke
D000818:Animals; D001345:Autoradiography; D002540:Cerebral Cortex / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000187:drug effects*; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000187:drug effects*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D003042:Cocaine