mPFC Subregions Research Articles

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 for the initiation of behavioural sensitization. Since the mPFC is not a homogenous structure, we attempted to systematically examine the contribution of the different subareas - infralimbic (il), prelimbic (pl), anterior cingulate (cg) - of the mPFC to the induction of sensitization by selectively lesioning these areas or the whole mPFC with quinolinic acid (45 nmol in 0.5 microl). During an initial habituation session only il 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 cocaine (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 and 2 weeks of withdrawal. None of the lesions affected the development of amphetamine-induced sensitization in any way, as assessed by several behavioural parameters including locomotion and sniffing. In contrast, cocaine-induced 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 sensitization, and only the pl area appears to be of relevance for cocaine-induced sensitization. It is suggested that these differences are due to differences in the pharmacological interaction of cocaine and amphetamine with the mesocortical dopamine system, and to the particular anatomical connections of each of the mPFC subregions.

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 accumbens septi and the ventral tegmental area have received much attention, their efferent and afferent structures have not been investigated to the same degree. One major input to this system originates from the medial prefrontal cortex (mPFC) which is not a homogenous structure but can be divided into different subareas that can be distinguished on anatomical and possibly functional grounds. We examined the effects of discrete bilateral quinolinic acid lesions (45 nmol/0.5 micro(L)) of each of the mPFC subareas, the infralimbic (il), prelimbic (pl) and the anterior cingulate (cg) mPFC, on the conditioned place preference (CPP) and psychomotor activation induced by several drugs. Lesions of the il mPFC blocked CPP induced by morphine (10 mg/kg) and CGP37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentic acid, a competitive N-methyl-D-aspartate receptor antagonist; 10 mg/kg]. Lesions of the pl mPFC 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 blocked morphine-, cocaine- and CGP37849-induced CPP. None of the lesions affected DL-amphetamine (4 mg/kg)-induced CPP. During the conditioning period, none of the lesions affected amphetamine-induced psychomotor activation and sensitization, whereas both phenomena were attenuated by pl and whole mPFC lesions in the case of cocaine, and by il and whole mPFC lesions in the case of morphine. These results show that the different mPFC subregions have distinct functional roles in the generation of behavioural effects produced by different classes of drugs. This heterogeneity should be taken into account in future studies addressing the role of the mPFC in drug reward and sensitization.

Effects of electrolytic lesions of the medial prefrontal cortex or its subfields on 4-arm baited, 8-arm radial maze, two-way active avoidance and conditioned fear tasks in the rat

The present study tested the effects of electrolytic lesions in two mPFC subregions, the dorsal anterior cingulate area (dACA) and prelimbic cortex, as well as the effects of a larger medial prefrontal cortex (mPFC) lesion which included both subregions, on 4-arm baited, 4-arm unbaited, 8-arm radial maze task and its reversal (Experiments 1 and 4), two-way active avoidance (Experiments 2 and 5) and conditioned emotional response (Experiments 3 and 6). Rats with large or small lesions of the mPFC learned the location of the 4 baited arms in the training and reversal stages of the radial maze task similarly to sham rats, indicating that these lesions did not affect animals' capacity to process and remember spatial information. dACA and mPFC lesions produced a transient deficit in the acquisition of the radial maze task, suggestive of an involvement of these regions in mnemonic processes. However, in view of the normal performance of these groups by the end of training and during reversal, this deficit is better interpreted as stemming from a difficulty to learn the memory-based strategy used to solve the task. Only mPFC lesion led to better avoidance performance at the beginning of training and tended to increase response during the presentation of a stimulus previously paired with shock, compared to sham rats. Both effects can be taken as an indication of reduced emotionality following mPFC lesion. The results are discussed in relation to known behavioral functions of the mPFC and the suggested functional specialization within this region.

Electrolytic lesions of the medial prefrontal cortex in rats disrupt performance on an analog of the Wisconsin Card Sorting Test, but do not disrupt latent inhibition: implications for animal models of schizophrenia

The effects of electrolytic lesions of the medial prefrontal cortex (mPFC) or its subregions were investigated on two cognitive tests that may have relevance to the behavioral impairments of patients with schizophrenia. One task consisted of a delayed nonmatch-to-sample and reversal of the non-match-to-sample rule, in a Skinner box. The reversal component simulated the essential feature of rule shifting of the Wisconsin Card Sorting Test (WCST), which is a commonly used test for assessing lsfrontal-like’ deficits in schizophrenia. The second was latent inhibition, in which repeated pre-exposure to a stimulus without consequence retards subsequent associations with that stimulus. Latent inhibition is impaired in acute schizophrenic patients, and its disruption in the rat has been suggested to constitute an animal model of schizophrenia. Expts. 1 and 2 tested the effects of lesions of the dorsal anterior cingulate cortex (dACA) and mPFC, respectively, on the WCST analog. Expt. 3 tested the effects of lesions of the dACA or infralimbic cortex, and Expt. 4 tested the effects of mPFC lesion, on latent inhibition. Lesions of mPFC subregions had no effect. mPFC lesion produced transient deficits in the performance of the DNMS task and impaired the reversal from the nonmatch-to-sample to the match-to-sample rule, but left the latent inhibition effect intact. Possible relevance of this behavioral profile on mPFC lesion of the ‘frontal syndrome’ is discussed.