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The reinforcing effects of chronic D-amphetamine and morphine are impaired in a line of memory-deficient mice overexpressing calcineurin.: Role of calcineurin in the effects of drugs of abuse

Abstract : It has recently emerged that there is a commonality in the molecular mechanisms underlying long-term neuronal changes in drug addiction and those mediating synaptic plasticity associated with learning and memory. In the hippocampus, the calcium-calmodulin-dependent protein phosphatase calcineurin plays a pivotal role in the molecular mechanisms that underlie learning and memory functions. Transgenic mice that express an active form of calcineurin specifically in forebrain structures have previously been shown to have a deficit in the transition from short- to long-term memory. Here, we investigated the involvement of calcineurin in the motivational effects of amphetamine and morphine using this line of transgenic mice (CN98). Our results showed that amphetamine and morphine did not induce conditioned place preference in calcineurin-mutant mice, whereas food remained an efficient reinforcer. In addition, behavioural sensitization to these two drugs, as measured by horizontal locomotion, was disturbed in the transgenic mice. In contrast, neither the horizontal locomotion in response to acute D-amphetamine or morphine nor the somatic signs of morphine withdrawal were affected in calcineurin mutant mice compared to their wild-type littermates. Our data indicate that calcineurin-mediated protein dephosphorylation in the hippocampus is involved in the long-term effects of drugs of abuse without influencing the motivational response to a natural reward or the physical component of opioid withdrawal. The present results emphasize the essential role of hippocampal-dependent learning and memory in the development of drug addiction.
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https://www.hal.inserm.fr/inserm-00276426
Contributor : Catalina Betancur <>
Submitted on : Tuesday, April 29, 2008 - 4:05:41 PM
Last modification on : Monday, December 17, 2018 - 1:30:54 AM
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Grazyna Biala, Catalina Betancur, Isabelle Mansuy, Bruno Giros. The reinforcing effects of chronic D-amphetamine and morphine are impaired in a line of memory-deficient mice overexpressing calcineurin.: Role of calcineurin in the effects of drugs of abuse. European Journal of Neuroscience, Wiley, 2005, 21 (11), pp.3089-96. ⟨10.1111/j.1460-9568.2005.04132.x⟩. ⟨inserm-00276426⟩

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