A role for the prefrontal cortex in heroin-seeking after forced abstinence by adult male rats but not adolescents.
Adolescent drug abuse is hypothesized to increase the risk of drug addiction. Yet male rats that self-administer heroin as adolescents show attenuated drug-seeking after abstinence, compared with adults. Here we explore a role for neural activity in the medial prefrontal cortex (mPFC) in age-dependent heroin-seeking. Adolescent (35-day-old at start; adolescent-onset) and adult (86-day-old at start) male rats acquired lever-pressing maintained by heroin using a fixed ratio one reinforcement schedule (0.05 and 0.025 mg/kg per infusion). Following 12 days of forced abstinence, rats were tested for heroin-seeking over 1 h by measuring the number of lever presses on the active lever. Unbiased stereology was then used to estimate the number of Fos-ir(+) and Fos-ir(-) neurons in prelimbic and infralimbic mPFC. As before, adolescents and adults self-administered similar amounts of heroin, but subsequent heroin-seeking was attenuated in the younger rats. Similarly, the adolescent-onset group failed to show significant neural activation in the prelimbic or infralimbic mPFC during the heroin-seeking test, whereas the adult-onset heroin self-administration group showed two to six times more Fos-ir(+) neurons than their saline counterparts in both mPFC subregions. Finally, the overall number of neurons in the infralimbic cortex was greater in rats from the adolescent-onset groups than adults. The mPFC may thus have a key role in some age-dependent effects of heroin self-administration.
Neuroscience Institute, Georgia State University, Atlanta, GA 30302-5030, USA.
James M
JM
Doherty
Bradley M
BM
Cooke
Kyle J
KJ
Frantz
D000367:Age Factors; D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism* / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D003932:Heroin / Q000008:administration & dosage*; D006556:Heroin Dependence / Q000378:metabolism* / Q000523:psychology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration
D003932:Heroin