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Differential effects of calcineurin inhibition and protein kinase A activation on nucleus accumbens amphetamine‐produced conditioned place preference in rats
Author(s) -
Gerdjikov Todor V.,
Beninger Richard J.
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04256.x
Subject(s) - conditioned place preference , nucleus accumbens , amphetamine , calcineurin , pharmacology , protein kinase a , chemistry , medicine , endocrinology , kinase , dopamine , biochemistry , transplantation , morphine
Abstract 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 µg in 0.5 µL per side) led to a significant amphetamine CPP in rats receiving four but not two training sessions; the 5.0‐µg dose had no effect on rats trained with eight sessions. Injections of the PKA activator Sp‐cAMPS (2.5 or 10.0 µg in 0.5 µL 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.