An activator of protein kinase C also augmented interactions between ethanol and GABA receptors. We reported that in the nucleus accumbens, which also contains opioid peptides, opiates and ethanol presynaptically decreased glutamatergic EPSPs and that naloxone inhibited both effects. These multiple ethanol actions, metabotropic regulations, and neuroadaptations could underlie relapse in abstaining alcoholics. Our previous studies, showing that acamprosate, which reduces such relapse, increased NMDA-EPSPs and inhibited presynaptic GABA B receptors, support this possibility. Glutamatergic synapses in the nucleus accumbens could be major substrates for opiate reward.
NMDA receptors play a role in opiate dependence.
Metabotropic glutamate receptor agonists reduced NMDA-EPSPs via presynaptic group 2 metabotropic receptors and reduced responses to exogenous NMDA via postsynaptic group 3 receptors. Moreover, presynaptic inhibitory effects of group 2 metabotropic agonists, but not group 3 agonists, on NMDA-EPSP size were significantly increased in neurons obtained from the nucleus accumbens of rats treated with morphine for 1 week. These and other findings suggest that long-term treatment with morphine alters the composition of NMDA receptor subunits and that NMDA and metabotropic glutamate receptors contribute to morphine tolerance and dependence. Our new studies focus on the amygdala central nucleus, another region important in drug dependence. AIDS-related dementia may be due to neurotoxic effects of the HIV coat protein gp120.