Interactions between low concentrations of ethanol and nicotine on firing rate of ventral tegmental dopamine neurones.
This study investigated interactions between ethanol and nicotine on dopamine-sensitive neurone firing in the ventral tegmental area (VTA), recorded in midbrain slices. No changes in spontaneous activity of the neurones were seen with nicotine at 10, 25, or 100 nM; at 250 nM there was a small significant increase in firing rate. Ethanol, applied alone, caused a significant increase in firing rate at 40 mM and at 60 nM but not at 20 mM. Combinations of 10 or 25 nM nicotine with 20 or 40 mM ethanol did not result in increased firing rates compared with either drug alone. However, nicotine 100 nM plus ethanol 60 mM significantly increased the rate of spontaneous firing compared with that after either drug alone at these concentrations. In contrast, nicotine at 250 nM plus ethanol at 60 mM did not increase firing rate, compared with each drug alone. Ketanserin, 2 microM, prevented the potentiating effect of nicotine 100 nM plus ethanol 60 mM. The results show synergism between ethanol and nicotine at specific concentrations that are likely to be present in the brain during the behavioural effects of these drugs, but the interaction is complex and may involve multiple drug actions.
Department of Pharmacology, St. George's Hospital Medical School, Cranmer Terrace, London SW19 ORE, UK.
A
A
Clark
H J
HJ
Little
D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D000431:Ethanol; D009538:Nicotine; D004298:Dopamine