Withdrawal from chronic drug exposure may induce PKA-mediated synaptic plasticity. In rats, prolonged withdrawal from chronic cocaine increases corticotropin releasing factor (CRF)-mediated long-term potentiation (LTP) in the central nucleus of the amygdala. This effect is significantly decreased by the PKA inhibitor H89.104 Chronic opiate treatment depresses LTP in rat hippocampal CA1 neurons and increases PKA activity, which may represent compensatory actions since opioid receptors are coupled to inhibitory Gi/o proteins.95 After withdrawal from chronic opiate treatment, administration of PKA inhibitors or a single injection of morphine can reduce PKA levels and restore LTP.95 These data suggest that PKA is involved in the enhancement of amygdala LTP noted during withdrawal from chronic cocaine and in the depression of hippocampal LTP noted during chronic opiate treatment.
