Serotonin-dopamine interaction in the rat ventral tegmental area: an electrophysiological study in vivo.
Electrophysiological techniques were used to study the effects of various serotonin (5-HT) agonists and antagonists on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) of rats. Systemic administration of the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (1.25-80 micrograms/kg i.v.) increased the firing rate of the majority (75%) of DA cells studied and stimulated their bursting activity. A subpopulation (25%) of DA neurons was inhibited by 8-OH-DPAT. Selective lesions of 5-HT neurons by the neurotoxin 5-7-dihydroxytryptamine abolished completely the excitatory effect of 8-OH-DPAT on both firing rate and bursting activity of DA neurons. Microiontophoretic application of 8-OH-DPAT into the VTA did not cause any change in the firing rate of DA neurons. Treatment with the selective 5-HT1B agonist CGS 12066B (7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrolo[1,2-a] quinoxaline 1:2 maleate salt) (1.25-160 micrograms/kg i.v.) did not cause any change in basal firing rate of VTA DA cells. Systemic administration of trifluoromethylphenylpiperazine (TFMPP) (1.25-160 micrograms/kg i.v.) and m-chlorophenylpiperazine (mCPP) (1.25-320 micrograms/kg i.v.), two mixed 5-HT1B/5-HT1C receptor agonists, significantly reduced the firing rate of all VTA DA neurons studied. The effect of mCPP (maximal inhibition, 40%) was more pronounced compared to that of TFMPP (maximal inhibition, 25%). Microiontophoretic application of mCPP into the VTA caused a marked inhibition of the basal activity of DA neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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Istituto di Ricerche Farmacologiche Mario Negri, Chieti, Italy.
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D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D004298:Dopamine / Q000502:physiology*; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D004873:Ergolines; D010879:Piperazines; D011985:Receptors, Serotonin; C018406:1-(3-trifluoromethylphenyl)piperazine; D012701:Serotonin; C047975:cyanopindolol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol; C015068:1-(3-chlorophenyl)piperazine; C031649:mesulergine; D004298:Dopamine