MODIFICATION OF SEROTONIN RESPONSES IN RAT DORSOLATERAL SEPTAL NUCLEUS NEURONS BY ACUTE AND CHRONIC COCAINE

We used standard intracellular current-clamp electrophysiological reco rding techniques in a brain slice preparation to determine whether chr onic cocaine administration would: 1) alter the sensitivity of septal neurons to exogenous serotonin (5-HT) application and 2) modify the in teraction of 5-HT with cocaine in vitro. Recordings were made from neu rons in rat brain slices that contained the dorsolateral septal nucleu s obtained from drug naive (DN) rats or rats given cocaine (15 mg/kg, i.p., 2 x daily) for periods of 7 (CC7) or 14 (CC14) days. In addition , some of these rats also received intraventricular pertussis toxin (P TX) injections 2 to 3 days before experimentation to abolish the posts ynaptic 5-HT1A receptor-mediated membrane hyperpolarization and to unm ask a 5-HT-induced depolarization. In comparison with DN and CC7, CC14 slices showed an increased sensitivity to 5-HT as revealed by a 2-fol d leftward shift in the 5-HT EC(50) values. In addition, in PTX-CC14 s lices, 5-HT could hyperpolarize the cell membrane, whereas the 5-HT1A agonist, 8-OH-DPAT, and the gamma-aminobutyric acid(B) agonist, baclof en, failed to do so. We also observed that cocaine (3 mu M) in CC14 sl ices did not significantly potentiate and prolong 5-HT hyperpolarizati ons as found in DN slices. We conclude that in the CC14 septal slice a 5-HT transporter is down-regulated and that an atypical 5-HT response can be elicited. Additionally, 5-HT1A receptor up-regulation and/or 5 -HT, receptor down-regulation may contribute to the increased sensitiv ity of septal neurons to 5-HT.