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.
Tzschentke
T M
TM
Department of Neuropharmacology, Zoological Institute, University of Tübingen, Mohlstrasse 54/1, D-72074 Tübingen, Germany. rincewind8@hotmail.com
Schmidt
W J
WJ
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000633:toxicity; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity; D007839:Functional Laterality; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; D000661:Amphetamine; D017378:Quinolinic Acid; D003042:Cocaine