Electrophysiological actions of cocaine on noradrenergic neurons in rat locus ceruleus.
Extracellular microelectrode experiments were conducted to study the effects of cocaine HCl on the activity of spontaneously firing single locus ceruleus (LC) noradrenergic neurons in vivo. The responses of single identified noradrenergic LC neurons to the systemic (i.v.) administration of cocaine were observed over a wide range of doses (0.0625-2.0 mg/kg). The spontaneous activity of all LC neurons receiving doses greater than the threshold dose (0.0625 mg/kg) was inhibited in a dose-dependent manner. The local anesthetics, procaine and mepivacaine, did not affect LC neuronal activity, action potential amplitude or slope. The inhibitory effects of cocaine on spontaneous LC neuron activity was reversed by the subsequent i.v. administration of the specific alpha-2 adrenoceptor antagonist, piperoxone, but not the opiate receptor antagonist, naloxone. Pretreatment with another alpha-2 adrenoceptor antagonist, yohimbine (5 mg/kg i.p.), attenuated significantly the inhibition of spontaneous LC activity elicited by i.v. cocaine. Intravenous cocaine produced a brief increase in mean arterial pressure which did not appear to be correlated with the more sustained inhibition of LC neurons. Reserpine pretreatment (10 mg/kg i.p.) attenuated significantly the inhibitory effects of cocaine on LC activity. These results suggest that the inhibition of spontaneous LC neuron activity by i.v. cocaine is most likely mediated by an augmented action of catecholamines at central alpha-2 adrenoceptors and not by the local anesthetic effects of cocaine.
D000200:Action Potentials; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D008125:Locus Coeruleus / Q000166:cytology* / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D015016:Yohimbine; D011343:Procaine; D003042:Cocaine