Amphetamine-induced zif268 mRNA expression in the medial posterior nucleusaccumbens in cholecystokinin-A receptor mutant rats

Converging evidence supports a role for cholecystokinin (CCK) in modulating dopamine (DA)-mediated activity in the rat mesolimbic system. In particula r, CCK co-localized with mesolimbic DA cells originating in the ventral teg mental area potentiates DA function in the medial posterior nucleus accumbe ns (mpNA) through CCK-A receptors. Recently, a strain of rats lacking the C CK-A receptor, Otsuka Long Evans Tokushima Fatty (OLETF), has been discover ed making it possible to study the mesolimbic DA regulatory role of CCK-A r eceptors. Previous studies have shown that OLETF rats are less sensitive to amphetamine (AMPH)-induced behavioral effects compared to controls. To det ermine if this altered sensitivity is associated with decreased AMPH-induce d postsynaptic activation in the mpNA in OLETF rats, we performed the follo wing experiment. OLETF (CCK-A mutants) and Long Evans Tokushima Otsuka (LET O) rats (controls) were given subcutaneous injections of either saline or A MPH (5.0 mg/kg). One hour after injection all animals were sacrificed and a ctivation of the mpNA was assessed using in situ hybridization with antisen se probes for zif268 mRNA. AMPH treatment produced a significant up-regulat ion of zif268 mRNA expression in both OLETF and LETO rats (P less than or e qual to 0.0002), compared to saline treatment. However, AMPH had almost an identical effect on zif268 mRNA expression in the mpNA in both rat strains suggesting similar postsynaptic neural activation. The significance of this AMPH-induced zif268 mRNA expression in these two rat strains and its relat ionship to CCK function in the nucleus accumbens are discussed. (C) 2000 El sevier Science Ireland Ltd. All rights reserved.