The acute and chronic administration of (+/-)-8-hydroxy-2-(Di-n-propylamino)tetralin significantly alters the activity of spontaneously active midbrain dopamine neurons in rats: an in vivo electrophysiological study.
This study examined the effect of the acute and chronic systemic administration of (+/-)-8-Hydroxy-2-(Di-n-propylamino)Tetralin(8-OH-DPAT) on the number and firing pattern of spontaneously active dopamine (DA) neurons in the ventral tegmental area (VTA or A10) and substantia nigra pars compacta (SNC or A9) in anesthetized male rats. These parameters were measured using extracellular in vivo electrophysiology. A single s.c. injection of 0.01, 0.1, or 1 mg/kg of 8-OH-DPAT did not significantly alter the number of spontaneously active SNC DA neurons compared to vehicle-treated animals (controls). The acute administration of 0.01 or 0.1 mg/kg of 8-OH-DPAT did not significantly alter, whereas the 1 mg/kg dose significantly decreased the number of spontaneously active VTA DA neurons compared to controls. The acute administration of 8-OH-DPAT significantly increased the percentage of VTA DA neurons firing in a bursting pattern. In contrast, there was a significant decrease in the percentage of SNC DA neurons firing in a bursting pattern following the acute administration of 8-OH-DPAT. The number of spontaneously active SNC DA neurons was not significantly altered by the chronic s.c. administration of 8-OH-DPAT (0.01, 0.1, or 1 mg/kg s.c.) as compared to controls. However, the chronic s.c. administration of all doses of 8-OH-DPAT significantly decreased the number of spontaneously active VTA DA neurons compared to controls. The i.v. administration of (+)-apomorphine (50 microg/kg) did not reverse the 8-OH-DPAT-induced decrease in the number of spontaneously active VTA DA neurons, suggesting that this effect is unlikely due to depolarization blockade. The percentage of VTA DA neurons exhibiting burst firing was significantly increased by 0.01 and 0.1 mg/kg, but significantly decreased by 1 mg/kg of 8-OH-DPAT. Overall, the systemic administration of 8-OH-DPAT preferentially affects the activity of spontaneously active A10 DA neurons in rats.
Nakamura
Kazuhiko
K
Department of Psychiatry, Hamamatsu University School of Medicine 1-20-1, Handayama, Hamamatsu, 431-3192, Shizuoka, Japan.
Suzuki
Katsuaki
K
McCreary
Andrew C
AC
Ashby
Charles R
CR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage*; D000200:Action Potentials / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008297:Male; D008636:Mesencephalon / Q000166:cytology*; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage*
D018491:Dopamine Agonists; D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001058:Apomorphine; D004298:Dopamine