Population response of midbrain dopaminergic neurons to neuroleptics: further studies on time course and nondopaminergic neuronal influences

• Published in: The Journal of neuroscience Vol. 7; no. 3; pp. 629 - 633
• Main Authors: Chiodo, LA, Bunney, BS
• Format: Journal Article
• Language: English
• Published: Washington, DC Soc Neuroscience 01.03.1987; Society for Neuroscience
• Subjects: Animals; Antipsychotic Agents - pharmacology; Biological and medical sciences; Dopamine - physiology; Electrophoresis; Haloperidol - pharmacology; Male; Medical sciences; Mesencephalon - cytology; Mesencephalon - drug effects; Neurons - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Proglumide - pharmacology; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Inbred Strains; Time Factors; Rat; Neuroleptic; Dopamine antagonist; Rodentia; Oral administration; Electrophysiology; Inactivation; Depolarization; Vertebrata; Mammalia; Animal; Antipsychotic; Dopaminergic neuron; Drug interaction; Antagonist; Cholecystokinin; Neurotransmission; Biological receptor
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.07-03-00629.1987

In the present study, we examined the effects of the cholecystokinin receptor antagonist, proglumide, on the depolarization-induced inactivation of A9 and A10 dopaminergic neurons produced by repeated administration of a classical antipsychotic drug (dopamine receptor antagonist). In addition, we studied the nature of the effects of acute (1-48 hr) and long-term (7 month) treatment with the butyrophenone neuroleptic haloperidol on both the basal firing rate and population response of dopamine-containing neurons in these 2 regions. Acute oral administration of haloperidol (0.5 mg/kg) results, within 1 hr of administration, in an increase in both the firing rate and number of spontaneously active dopamine neurons encountered in both A9 and A10 regions. These effects of a single treatment persist for a minimum of 6 hr and, with respect to firing rate, are not completely normalized for at least 24 hr. In contrast, 7 month continuous treatment with haloperidol reduces the number of spontaneously active DA neurons encountered in both regions in a manner similar to that observed at 21 d. This effect is inferred to be due to the induction of depolarization-induced inactivation of these neurons, since the acute administration of the normally hyperpolarizing, direct-acting dopamine receptor agonist apomorphine (64 micrograms/kg) immediately reverses this reduced number of cells per track to near control levels. This effect appears to be dependent on the continued presence of haloperidol since, when animals treated for 7 months are sampled 14 d after the cessation of drug administration, spontaneous activity is no different from that observed in age-matched controls.