Reduced dopamine (DA) D2-class receptor (D2R) mediation of excitability in medial prefrontal cortex (mPFC) pyramidal neurons after repeated cocaine administration

Washington DC

Congreso; 2005 Society for Neuroscience Meeting; 2005

The mPFC is a forebrain region which receives DA innervation and is involved in acquisition of self-administration and withdrawal effects of cocaine. Both DA D1R and D2R participate in regulation of neuronal activity in the mPFC. Previous studies reveal that chronic exposure to cocaine decreases neuronal activity in the PFC of drug abusers during withdrawal, whereas the decreased PFC activity is reversed when those abusers are challenged with a dose of cocaine-like drug or by drug-related memory. These results correspond to our recent findings, in which the increased excitability is observed in drug-withdrawn mPFC neurons of rats in response to certain excitatory stimuli. Although previous studies have determined that D2R stimulation suppresses evoked firing in mPFC pyramidal neurons, it is unknown whether this effect of D2Rs on excitability is altered in those cocaine-withdrawn mPFC neurons. This study was therefore designed and performed to answer this question. Whole-cell current clamp recordings were used in visually-identified layer V-VI mPFC pyramidal neurons in brain slice preparations. Rats received repeated administration of cocaine (15mg/kg/day, i.p.) or saline (0.1ml/100g) for 5 consecutive days followed by 3 weeks of withdrawal. D2R stimulation by bath-applied quinpirole (1 μM) significantly decreased evoked Na+ spikes in saline-withdrawn neurons, along with an increased rheobase and reduced spike amplitude. However, these inhibitory effects of D2R stimulation on mPFC neurons were abolished in cocaine-withdrawn neurons. These findings indicate that D2R mediation of the excitability in mPFC pyramidal neurons is diminished after repeated cocaine administration with 3 weeks of withdrawal. They also suggest that a down-regulation of D2Rs may contribute to the alterations in the excitability of cocaine-withdrawn mPFC neurons.