Journal of Neurophysiology, Vol 73, Issue 2 687-692, Copyright © 1995 by APS
Cocaine prolongs norepinephrine synaptic potentials in rat dorsal raphe
S. Oleskevich and J. T. Williams
Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201, USA.
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.
