title: Ventral tegmental area: site through which dopamine D2-receptor agonists evoke behavioural and electrocortical sleep in rats.
abstract: 1. In freely moving rats the effects on behaviour and electrocortical (ECoG) spectrum power of some dopamine agonists, i.e. apomorphine and (+)-3PPP, given directly into different areas of the rat brain were studied. In particular, dopamine agonists were microinfused in the ventral tegmental area (VTA) and substantia nigra (SN) or into the caudate nucleus, n. accumbens and prefrontal cortex. The ECoG spectrum power effects were continuously analysed by means of a computerized Berg-Fourier analyser as total spectrum power and power in preselected frequency bands. 2. Apomorphine and (+)-3PPP (0.01, 0.1 and 1.0 nmol) given bilaterally into the VTA produced behavioural and ECoG sleep in a dose-dependent fashion. A statistically significant (P less than 0.01) increase in ECoG total spectrum power with a predominant increase in the lower frequency bands (0.25-3, 3-6 and 6-9 Hz) occurred. No behavioural and ECoG changes were evoked by the same doses of apomorphine bilaterally microinfused into the SN or into the caudate nucleus or by (+)-3PPP (1.0 nml) microinjected into the n. accumbens or applied onto the prefrontal cortex. 3. Behavioural and ECoG sleep was also induced in rats after systemic administration of apomorphine (263 nmol kg-1, i.p.). 4. The behavioural and ECoG spectrum power effects of apomorphine (1.0 nmol) bilaterally micro-infused into the VTA were prevented by a previous microinjection into the same site of (-)-sulpiride (9.8 nmol). Similarly, behavioural and ECoG effects evoked by (+)-3PPP (0.1 nmol) given bilaterally into the VTA, were completely antagonized by a previous injection into the same site of haloperidol (16 pmol given 10 min before). In contrast, pretreatment with SCH 23390 (50 pgkg-1, s.c.), a selective antagonist at dopamine Dl-receptors, was unable to antagonize the behavioural and ECoG spectrum power effects of ( +)-3PPP. 5. Soporific effects induced by systemic administration of apomorphine were antagonized by (-)- sulpiride (9.8 nmol) given bilaterally into the VTA 10min before, whereas, yohimbine (1.3 nmol), (an antagonist at alpha 2-adrenoceptors) bilaterally microinfused into the VTA, was ineffective in this respect. 6. The present experiments provide evidence suggesting that stimulation of dopamine D2-receptors located at the cell body level and/or the dendrites of dopaminergic neurones in the VTA may represent the mechanism through which apomorphine or (+)-3PPP exert their soporific effects in rats.
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, University of Reggio Calabria, Catanzaro, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bagetta
authors.forename: G
authors.initials: G
authors.lastname: De Sarro
authors.forename: E
authors.initials: E
authors.lastname: Priolo
authors.forename: G
authors.initials: G
authors.lastname: Nisticò
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D004569:Electroencephalography; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2; D012890:Sleep / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*
chemical_list: D010880:Piperidines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013469:Sulpiride; C026539:preclamol; D001058:Apomorphine