Differential effects of discrete subarea-specific lesions of the rat medial prefrontal cortex on amphetamine- and cocaine-induced behavioural sensitization

The medial prefrontal cortex (mPFC) of the rat is thought to be important f or the initiation of behavioural sensitization. Since the mPFC is not a hom ogenous structure, we attempted to systematically examine the contribution of the different subareas - infralimbic (il), prelimbic (pl), anterior cing ulate (cg) - of the mPFC to the induction of sensitization by selectively l esioning these areas or the whole mPFC with quinolinic acid (45 nmol in 0.5 mu l). During an initial habituation session only ii or whole mPFC lesions reduced spontaneous activity. Lesioned and sham-lesioned animals were then treated every other day with either saline, DL amphetamine (3 mg/kg), or c ocaine (20 mg/kg) for 2 weeks in their home cages and were then challenged with either DL-amphetamine (1.5 mg/kg) or cocaine (10 mg/kg) after 1 day an d 2 weeks of withdrawal. None of the lesions affected the development of am phetamine induced sensitization in any way, as assessed by several behaviou ral parameters including locomotion and sniffing. In contrast, cocaine-indu ced sensitization was significantly attenuated by pl and whole mPFC lesions , while il and cg lesions were without effect. These results show a double dissociation of the role of the mPFC in behavioural sensitization. The mPFC seems to be important only for cocaine- but not for amphetamine induced se nsitization, and only the pl area appears to be of relevance for cocaine in duced sensitization. It is suggested that these differences are due to diff erences in the pharmacological interaction of cocaine and amphetamine with the mesocortical dopamine system, and to the particular anatomical connecti ons of each of the mPFC subregions.