title: Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro.
abstract: Intracellular recordings of membrane potential were made from neurons in nucleus dorsal raphe in the rat brain slice. Cocaine (300 nM-30 microM) caused a concentration-dependent hyperpolarization of the membrane potential, with a maximum effect of 13.3 +/- 2.2 mV (N = 6) and an EC50 of 4.2 microM. This action was antagonized by spiperone (1 microM), suggesting that the hyperpolarization was mediated indirectly through endogenous 5-hydroxytryptamine (5-HT). Cocaine (300 nM) increased the time constant for decay (tau 2) of the 5-HT inhibitory postsynaptic potential (IPSP) from 432 +/- 57 msec to 708 +/- 81 msec (N = 14); 10 microM increased tau 2 by about 9-fold. Amphetamine (100 nM-10 microM) caused a depolarization that was antagonized by prazosin (100 nM). In slices taken from reserpine-treated animals (5 mg/kg, 12 hr), the 5-HT-mediated IPSP, the noradrenaline-mediated slow excitatory postsynaptic potential and the amphetamine-induced depolarization were absent. These results indicate that the amphetamine-induced depolarization resulted from the release of endogenous noradrenaline. In the presence of prazosin (100 nM), amphetamine caused a hyperpolarization at a threshold concentration of 10 microM, had an EC50 of 26 microM and a maximum effect of 10 +/- 0.9 mV (N = 8). This hyperpolarization as well as the cocaine-induced hyperpolarization were not reduced by prior treatment with reserpine. Amphetamine (10 microM) caused a 2.2-fold increase in the time constant of decay of the IPSP with no change in the amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Vollum Institute, Oregon Health Science University, Portland.
authors: Z Z
authors: ZZ
authors: Pan
authors: J T
authors: JT
authors: Williams
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects*; D051381:Rats; D012701:Serotonin / Q000502:physiology; D013134:Spiperone / Q000494:pharmacology
chemical_list: D012701:Serotonin; D013134:Spiperone; D000661:Amphetamine; D003042:Cocaine; D011224:Prazosin