title: Electrophysiological characterization of dopamine neuronal activity in the ventral tegmental area across the light-dark cycle.
abstract: Direct evidence that dopamine (DA) neurotransmission varies during the 24 h of the day is lacking. Here, we have characterized the firing activity of DA neurons located in the ventral tegmental area (VTA) using single-unit extracellular recordings in anesthetized rats kept on a standard light-dark cycle. DA neuronal firing activity was measured under basal conditions and in response to intravenous administration of increasing doses of amphetamine (AMPH: 0.5, 1, 2, 5 mg/kg), apomorphine (APO: 25, 50, 100, 200 µg/kg) and melatonin (MLT: 0.1, 1, 10 mg/kg) at different time intervals of the light-dark cycle. DA firing activity peaked between 07:00 and 11:00 h (3.5 ± 0.3 Hz) and between 19:00 and 23:00 h (4.1 ± 0.7 Hz), with lowest activity occurring between 11:00 and 15:00 h (2.4 ± 0.2 Hz) and between 23:00 and 03:00 h (2.6 ± 0.2 Hz). The highest number of spontaneously active neurons was observed between 03:00 and 06:00 h (2.5 ± 0.3 neurons/track), whereas the lowest was between 19:00 and 23:00 h (1.5 ± 0.2 neurons/track). The inhibitory effect of AMPH on DA firing rate was similar in both phases. The inhibitory effect of low dose of APO (25 μg/kg, dose selective for D2 autoreceptor) was more potent in the dark phase, whereas APO effects at higher doses were similar in both phases. Finally, MLT administration (1 mg/kg) produced a moderate inhibition of DA cell firing in both phases. These experiments demonstrate the existence of an intradiurnal rhythmic pattern of VTA DA neuronal firing activity and a higher pharmacological response of D2 autoreceptors in the dark phase.
authors: Department of Psychiatry, Neurobiological Psychiatry Unit, McGill University, Montreal, Quebec, H3A 1A1, Canada.
authors: Sergio
authors: S
authors: Domínguez-López
authors: Rebecca Dean
authors: RD
authors: Howell
authors: Martha Graciela
authors: MG
authors: López-Canúl
authors: Marco
authors: M
authors: Leyton
authors: Gabriella
authors: G
authors: Gobbi
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D008839:Microelectrodes; D017440:Photoperiod; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D002492:Central Nervous System Depressants; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D000661:Amphetamine; D008550:Melatonin; D001058:Apomorphine
keywords: amphetamine; apomorphine; cosinor; diurnal rhythm; firing activity