Cocaine decreases the glycine-induced Cl − current of acutely dissociated rat hippocampal neurons

Abstract

The effects of cocaine on glycine-induced Cl − current ( I GLY) of single neurons, freshly isolated from the rat hippocampal CA1 area, were studied with conventional whole-cell recording under voltage-clamp conditions. Cocaine depressed I GLY in a concentration-dependent manner, with an IC 50 of 0.78 mM. Preincubation with 1 mM cocaine alone had no effect on I GLY, suggesting that resting glycine channels are insensitive to cocaine. The depression of I GLY by cocaine was independent of membrane voltage. Internal cell dialysis with 1 mM cocaine failed to modify I GLY. Because the depression of I GLY was noncompetitive, cocaine may act on the glycine receptor–chloride ionophore complex at a site distinct from that to which glycine binds. The cocaine suppression of I GLY was unaffected by 1 μM tetrodotoxin and 1 μM strychnine. Blockers of protein kinase C (Chelerythrine), kinase A ( N-[2-(( p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide HCl, (H-89)) and Ca-calmodulin-dependent kinase (1-[ N, O-bis(5-isoquinolinesulfonyl)- N-methyl- l-tyrosyl]-4-phenylpiperazine (KN-62)) were also ineffective, which suggests that these phosphorylating mechanisms do not modulate cocaine-induced suppressant action on I GLY. This extracellular, strychnine-independent depression of I GLY may contribute to cocaine-induced seizures.