Effects of cocaine on the serotonin-induced inward current in rat nodose ganglion neurons.
Application of 5-hydroxytryptamine (5-HT) to freshly isolated rat nodose ganglion neurons produced a fast inward current when measured using the whole-cell patch-clamp technique. This current was blocked by the 5-HT3 receptor antagonist MDL72222. The selective 5-HT3 receptor agonist 2-methyl-5-HT induced a similar current. Cocaine (0.1-300 microM) applied simultaneously with 5-HT (0.25-50 microM) inhibited the 5-HT-induced current. The inhibition did not appear to be voltage dependent. If cocaine was preapplied for about 30 sec, the effect of cocaine on 5-HT current was increased. Both the peak and the steady-state 5-HT current was depressed by cocaine. However, the peak current was more sensitive to cocaine than the steady-state current. The concentration-response curves of cocaine in different agonist concentrations revealed that cocaine competitively inhibited the 5-HT3 receptor-mediated current with a pA2 value of 5.8 and an apparent KD of 1.6 microM. These results suggest that in addition to the other well known mechanisms, the 5-HT3 receptor-ion channel complex is another site for cocaine action.
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Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland.
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D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009620:Nodose Ganglion / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012701:Serotonin; D003042:Cocaine