TY - JOUR T1 - Chronic Cocaine Enhances γ-Aminobutyric Acid and Glutamate Release by Altering Presynaptic and not Postsynaptic γ-Aminobutyric Acid<sub>B</sub> Receptors within the Rat Dorsolateral Septal Nucleus JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 129 LP - 137 VL - 280 IS - 1 AU - Shingo Shoji AU - Debra Simms AU - Wesley C. McDaniel AU - Joel P. Gallagher Y1 - 1997/01/01 UR - http://jpet.aspetjournals.org/content/280/1/129.abstract N2 - Cocaine is a popular and sometimes deadly drug of abuse. Its mechanisms of action have previously not been linked with receptors localized to presynaptic sites for the major central nervous system amino acid transmitters γ-aminobutyric acid (GABA) and glutamate. We demonstrate that, within the dorsolateral septal nucleus of in vitrobrain slices from animals that had received cocaine chronicallyin vivo for 14 or 28, but not 7, days, control of both inhibitory (GABA) and excitatory (glutamate) amino acid transmission is impaired, due to the combined diminished effectiveness of presynaptic GABAB auto- and heteroreceptors. As a result, disinhibition of inhibitory and excitatory transmitters occurs, with enhanced transmitter release. Although the involvement of postsynaptic GABAB receptors has been suggested in the chronic actions of cocaine at other central nervous system nuclei, we do not see any change in the effectiveness of the postsynaptic GABABreceptors within the dorsolateral septal nucleus. Modulation of presynaptic GABAB receptors at central nervous system nerve terminals after chronic cocaine administration has not been reported previously. Our findings demonstrate that chronic intermittent cocaine administration for at least 14 days induces a persistent change in neuronal activity that involves both inhibitory and excitatory amino acid-mediated transmission within the dorsolateral septal nucleus. These results suggest that nerve terminal GABAB receptors have been overlooked as playing a role in either the etiology and treatment of chronic cocaine addiction or cocaine toxicity. The American Society for Pharmacology and Experimental Therapeutics ER -