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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
Author(s) -
Lynch W. J.,
Taylor J. R.
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.1460-9568.2005.04305.x
Subject(s) - nucleus accumbens , addiction , protein kinase a , pharmacology , chemistry , psychology , neuroscience , medicine , endocrinology , dopamine , kinase , biochemistry
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.