Differential effects of calcineurin inhibition and protein kinase A activation on nucleus accumbens amphetamine-produced conditioned place preference in rats.
The nucleus accumbens (NAc) plays a critical role in amphetamine-produced conditioned place preference (CPP). In previous studies inhibition or activation of cyclic adenosine monophosphate-dependent protein kinase (PKA) blocked NAc amphetamine-produced CPP. PKA activation unrelated to ongoing DA transmission may disrupt reward-related learning. Calcineurin (CN) down-regulates downstream PKA targets. Unlike PKA activation, CN inhibition may preserve and enhance reward-related learning. The PKA signalling cascade is negatively regulated by calcineurin (CN). We tested the hypothesis that post-training CN inhibition in NAc will enhance NAc amphetamine-produced CPP and that PKA activation will block CPP. Eight but not four or two 30-min conditioning sessions were sufficient to establish significant CPP. Immediate post-training, NAc injection of the calcineurin inhibitor FK506 (5.0 but not 1.0 microg in 0.5 microL per side) led to a significant amphetamine CPP in rats receiving four but not two training sessions; the 5.0-microg dose had no effect on rats trained with eight sessions. Injections of the PKA activator Sp-cAMPS (2.5 or 10.0 microg in 0.5 microL per side) failed to affect CPP following two or four training sessions and blocked CPP produced by a standard 8-day conditioning schedule. Results suggest that CN acts as a negative regulator in the establishment of NAc amphetamine-produced CPP, a form of reward-related learning.
Gerdjikov
Todor V
TV
Department of Psychology, Queen's University, Kingston, ON K7L 3N6, Canada.
Beninger
Richard J
RJ
D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects; D007839:Functional Laterality; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013997:Time Factors
D000697:Central Nervous System Stimulants; D047428:Protein Kinase Inhibitors; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; D000661:Amphetamine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin; D016559:Tacrolimus