OPIOID EFFECTS ON CA-45(2-CORTEX IN PRIMARY CULTURE() UPTAKE AND GLUTAMATE RELEASE IN RAT CEREBRAL)

Primary cultures of rat cortex, conveniently prepared from newborn ani mals, were used to study opioid effects on Ca-45(2+) uptake and glutam ate release, Ca-45(2+) uptake, induced by treatment with glutamate or NMDA, was largely blocked by the NMDA antagonist MK-801, KC depolariza tion-induced Ca-45(2+) uptake was also reduced by MK-801, indicating t hat the effect was mediated by glutamate release, Direct analysis veri fied that glutamate, and aspartate, were indeed released, Opioid pepti des of the prodynorphin system were also released and these, or other peptides, were functionally active, because naloxone treatment increas ed glutamate release, as well as the Ca-45(2+) uptake induced by depol arization, Opioid agonists, selective for mu-, kappa-, and delta-recep tors, inhibited the Ca-45(2+) uptake induced by K+ depolarization, The combination of low concentrations of MK-801 and opioid agonists resul ted in additive inhibition of K+- induced Ca-45(2+) uptake, The result s indicate that this system may be useful as an in vitro CNS model for studying modulation by opioids of glutamate release and Ca2+ uptake u nder acute, and perhaps also chronic, opiate treatment.