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Persistent changes in motivation to self-administer cocaine following modulation of cyclic AMP-dependent protein kinase A (PKA) activity in the nucleus accumbens


  • W. J. Lynch,

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      Current address: Department of Psychiatric Medicine, University of Virginia Health Sciences, P.O. Box 800623, Charlottesville, VA 22908, USA.

  • J. R. Taylor

    1. Department of Psychiatry, Yale University School of Medicine, CMHC, Abraham Ribicoff Research Facilities, 34 Park Street, New Haven, CT 06508, USA
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Dr Wendy J. Lynch, as above.


Drug-induced neuroadaptations within the nucleus accumbens, including activation of cAMP-dependent protein kinase A (PKA), may contribute to the synaptic plasticity and behavioural changes that underlie drug addiction. As a direct test of this hypothesis, we examined the effects in rats of PKA activation (Sp-cAMPS infusions of 10 and 20 nmol/side) and inhibition (Rp-cAMPS infusions of 10 and 20 nmol/side) in the nucleus accumbens on motivation to obtain cocaine as measured by responding under the progressive-ratio schedule. Bilateral infusions of Sp-cAMPS (20 nmol/side) resulted in an increase in progressive-ratio responding for cocaine and this effect persisted for several days. In contrast, Rp-cAMPS (20 nmol/side) produced persistent decreases in progressive-ratio responding for cocaine beginning on the day of administration and lasting for several days. These data suggest that alternations in PKA activity within the nucleus accumbens as a consequence of repeated cocaine exposure may contribute to addiction by producing persistent increases in motivation to obtain cocaine.

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