title: Antagonism by WAY-100635 of the effects of 8-OH-DPAT on performance on a free-operant timing schedule in intact and 5-HT-depleted rats.
abstract: In this experiment we examined the effect of a serotonin receptor (5-HT1A) agonist and antagonist WAY-100635 (N-[2-(4-[2-methoxy-phenyl]-1-piperazinyl)ethyl]-N-2-pyridinylcyclohexane-carboxamide) on temporal differentiation, in intact rats and rats whose serotonergic (5-HTergic) pathways had been destroyed by 5,7-dihydroxytryptamine (5,7-DHT). Thirteen rats received 5,7-DHT-induced lesions of the median and dorsal raphe nuclei; 14 rats received sham lesions. They were trained to press two levers (A and B) in 50-s trials, in which reinforcement was contingent upon responding on A in the first half, and B in the second half, of the trial. Logistic psychophysical curves were fitted to the relative response rate data (percent responding on B, %B), for derivation of timing indices [T50 (time corresponding to %B=50%), slope, Weber fraction] following WAY-100635, 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin], combinations of WAY-100635+8-OH-DPAT, and vehicle alone. WAY-100635 (30, 100 and 300 microg/kg, s.c.) did not affect the timing indices. 8-OH-DPAT (100, 200 microg/kg, s.c.) reduced T50 without affecting the Weber fraction. WAY-100635 (300 microg/kg) abolished the effect of 8-OH-DPAT on T50 in both the lesioned and sham-lesioned groups. 5-HT levels in the neocortex, hippocampus, amygdala, nucleus accumbens and hypothalamus of the lesioned group were <20% of those in the sham-lesioned group; catecholamine levels were unaffected. The results confirm that 8-OH-DPAT disrupts temporal differentiation in a free-operant psychophysical schedule, reducing T50, and indicate that this effect of 8-OH-DPAT is mediated by postsynaptic 5-HT1A receptors.
authors.affiliation: Psychopharmacology Section, Division of Psychiatry, University of Nottingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Body
authors.forename: S
authors.initials: S
authors.lastname: Kheramin
authors.forename: S
authors.initials: S
authors.lastname: Mobini
authors.forename: M-Y
authors.initials: MY
authors.lastname: Ho
authors.forename: D N
authors.initials: DN
authors.lastname: Velazquez-Martinez
authors.forename: C M
authors.initials: CM
authors.lastname: Bradshaw
authors.forename: E
authors.initials: E
authors.lastname: Szabadi
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D005260:Female; D005508:Food Deprivation; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013998:Time Perception / Q000187:drug effects*
chemical_list: D015306:Biogenic Monoamines; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin