Our newest studies focus on the amygdala, another region important in drug reward and dependence. Acute treatment with ethanol dramatically increased GABAergic inhibitory postsynaptic potentials in amygdala neurons obtained from rats after chronic treatment with ethanol and decreased glutamatergic EPSPs in amygdala slices obtained from both naive and ethanol-treated rats. These results indicate that ethanol alters both GABAergic and glutamatergic systems in the amygdala, with little tolerance after chronic ethanol treatment. These actions may represent cellular mechanisms of ethanol reward. Glutamatergic synapses in the nucleus accumbens also provide the mechanism that underlies opiate reward.
NMDA receptors play a role in opiate dependence.
Chronic treatment with morphine significantly increased presynaptic inhibitory effects of metabotropic receptor agonists on NMDA-EPSP size in neurons in the nucleus accumbens. These and other findings suggest that chronic treatment with morphine alters the composition of NMDA receptor subunits and that metabotropic receptors also contribute to morphine dependence. These and other data suggest that some neurons in the nucleus accumbens have strychnine-insensitive glycine receptors. Bicuculline and picrotoxin did not totally block GABA currents, suggesting that GABA could be the endogenous agonist for this receptor. In collaboration with I. Campbell, Department of Neuropharmacology, we are using transgenic mice to investigate the neuronal effects of cytokines.