Cocaine self-administration in rats differentially alters mRNA levels of the monoamine transporters and striatal neuropeptides

The potential neuroadoptations to cocaine self-administration (SA) were eva luated using quantitive in situ hybridisation histochemistry. Levels of mRN As of the nonoamine transporters, i.e. the primary molecular targets of coc aine, and the striatal neuropeptides substance P and enkephalin, which pred ominantly exist in different populations of dopaminoceptive striatal neuron s, were quantified in rats which had reached different stages of acquisitio n of cocaine SA. Thus, animals were killed 1 h after completing a self-admi nistration session ii early in or after acquisition of cocaine SA (ii) afte r various regimes of chronic cocaine Sh, and (iii) a 10-day period of withd rawal from chronic cocaine intake, Control mRNA levels of all molecules und er study were those quantified in animals receiving i.v. saline yoked to ra ts: self-administering cocaine (1.5 or 0.75 mg/kg per infusion, depending o n the experiment). Monoomine transporter expression was differentially alte red by cocaine; dopamine transporter mRNA levels in the ventral tegmental a rea, but not in the substantia nigra, were increased following withdrawal f rom cocaine, suggesting a role for the upregulated mesolimbic dopamine tran sporter in the mechanisms underlying relapse to cocaine taking. By contrast , serotonin transporter mRNA in the dorsal raphe and noradrenaline transpor ter mRNA in the locus coeruleus remained unaltered under all experimental c onditions. In addition, the expression of the striatal neuropeptides was al so differentially altered, substance P mRNA levels were transiently increas ed in the shell of the nucleus accumbens by prolonged cocaine self-administ ration. but enkephalin mRNA levels in the dorsal and ventral striatum remai ned unaltered under all conditions. (C) 2000 Elsevier Science B.V. All righ ts reserved.