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Repeated exposure to cocaine alters medial prefrontal cortex dopamine D 2 ‐like receptor modulation of glutamate and dopamine neurotransmission within the mesocorticolimbic system
Author(s) -
Liu Kun,
Steketee Jeffery D.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07362.x
Subject(s) - nucleus accumbens , quinpirole , ventral tegmental area , dopamine , prefrontal cortex , microdialysis , glutamatergic , medicine , endocrinology , glutamate receptor , neuroscience , dopaminergic , chemistry , psychology , receptor , cognition
J. Neurochem. (2011) 119 , 332–341. Abstract Repeated exposure to cocaine progressively increases drug‐induced locomotor activity, which is termed behavioral sensitization. Previous studies have demonstrated that sensitization to cocaine is associated with a decrease in dopamine D 2 receptor function in the medial prefrontal cortex. The present report tested the hypothesis that reduced medial prefrontal cortex D 2 receptor function as a result of repeated cocaine exposure results in augmented excitatory transmission to the nucleus accumbens and ventral tegmental area, possibly as a partial result of enhanced inhibition of local dopamine release. Dual probe microdialysis experiments were conducted in male Sprague–Dawley rats 1, 7 or 30 days following the last of four daily injections of saline (1.0 mL/kg) or cocaine (15 mg/kg). Infusion of quinpirole (0.01, 1.0 and 100 μM), a D 2 ‐like receptor agonist, into the medial prefrontal cortex produced a dose‐dependent decrease in cortical, nucleus accumbens and ventral tegmental area extracellular glutamate levels in control but not sensitized animals. Quinpirole also reduced basal dopamine levels in the medial prefrontal cortex in sensitized animals following 1 day of withdrawal from cocaine. Following 30 days of withdrawal, quinpirole also reduced dopamine levels in sensitized animals relative to saline controls, but not relative to baseline levels. These findings indicate that the expression of sensitization to cocaine is associated with altered modulation of mesocorticolimbic glutamatergic transmission at the level of the medial prefrontal cortex.