Cocaine prolongs norepinephrine synaptic potentials in rat dorsal raphe.
1. The effect of cocaine on the excitatory response to norepinephrine (NE) was investigated with the use of intracellular recording from rat dorsal raphe (DR) neurons in the slice preparation. 2. Focal stimulation evoked a slow excitatory postsynaptic potential (sEPSP) that was mediated by alpha 1-adrenoceptor activation. The sEPSP was studied in isolation with the use of a selective 5-HT1A receptor antagonist, pindobind 5HT1A, which eliminated the inhibitory postsynaptic potential (IPSP) that preceded the sEPSP. The sEPSP had a latency to peak of 6 s, a peak amplitude of 6 mV, and a time constant of decay (t) of 14 s. 3. Bath application of cocaine more than doubled the latency-to-peak (13 s) and the time constant of decay (29 s) and had no effect on the amplitude. 4. Iontophoretically applied NE produced a membrane potential depolarization with an amplitude and time course similar to the sEPSP (latency-to-peak = 10 s; peak amplitude = 5 mV; t = 20 s). Cocaine significantly increased the latency-to-peak and the time constant of decay of the depolarization induced by iontophoretically applied NE. 5. Superfusion with NE caused a concentration-dependent depolarization. Cocaine (1 microM) did not change the concentration response to NE. 6. These results suggest that cocaine enhances the excitatory action of NE in the dorsal raphe by a prolongation of the alpha 1-adrenoceptor-mediated sEPSP.
Oleskevich
S
S
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201, USA.
Williams
J T
JT
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D000081005:Cyclohexane Monoterpenes; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007478:Iontophoresis; D009638:Norepinephrine / Q000494:pharmacology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012702:Serotonin Antagonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*
D000081005:Cyclohexane Monoterpenes; D012702:Serotonin Antagonists; C084712:pindobind; D010869:Pindolol; D003042:Cocaine; D009638:Norepinephrine