Differential actions of cocaine and amphetamine on dorsal raphe neurons in vitro.
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)
Pan
Z Z
ZZ
Vollum Institute, Oregon Health Science University, Portland.
Williams
J T
JT
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
D012701:Serotonin; D013134:Spiperone; D000661:Amphetamine; D003042:Cocaine; D011224:Prazosin