Functional heterogeneity of the rat medial prefrontal cortex: effects of discrete subarea-specific lesions on drug-induced conditioned place preference and behavioural sensitization

While the principal components of the brain reward system, the nucleus accu mbens septi and the ventral tegmental area have received much attention, th eir efferent and afferent structures have not been investigated to the same degree. One major input to this system originates from the medial prefront al cortex (mPFC) which is not a homogenous structure but can be divided int o different subareas that can be distinguished on anatomical and possibly f unctional grounds. We examined the effects of discrete bilateral quinolinic acid lesions (45 nmol/0.5 mu L) of each of the mPFC subareas, the infralim bic (il), prelimbic (pl) and the anterior cingulate (cg) mPFC, on the condi tioned place preference (CPP) and psychomotor activation induced by several drugs. Lesions of the il mPFC blocked CPP induced by morphine (10 mg/kg) a nd CGP37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentic acid, a competiti ve N-methyl-D-aspartate receptor antagonist; 10 mg/kg]. Lesions of the pl m PFC blocked CPP induced by cocaine (15 mg/kg) and CGP37849, and lesions of the cg mPFC only blocked CGP37849-induced CPP. Lesions of the whole mPFC bl ocked morphine-, cocaine- and CGP37849-induced CPP, None of the lesions aff ected DL-amphetamine (4 mg/kg)-induced CPP. During the conditioning period, none of the lesions affected amphetamine-induced psychomotor activation an d sensitization, whereas both phenomena were attenuated by pi and whole mPF C lesions in the case of cocaine, and by ii and whole mPFC lesions in the c ase of morphine. These results show that the different mPFC subregions have distinct functional roles in the generation of behavioural effects produce d by different classes of drugs. This heterogeneity should be taken into ac count in future studies addressing the role of the mPFC in drug reward and sensitization.