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Differential effects of calcineurin inhibition and protein kinase A activation on nucleus accumbens amphetamine-produced conditioned place preference in rats.

By Todor V. Gerdjikov and Richard J. Beninger

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

Year: 2005
DOI identifier: 10.1111/j.1460-9568.2005.04256.x
OAI identifier: oai:lra.le.ac.uk:2381/2576
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