Behavioral and biochemical effects of the 5-HT1A receptor agonists flesinoxan and 8-OH-DPAT in the rat.
The 5-HT1A receptor agonists flesinoxan (0.2-3.2 mg kg-1 s.c.) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.025-0.4 mg kg-1 s.c.) produced (1) a dose-dependent facilitation of male rat ejaculatory behavior and (2) characteristic, dose-dependent effects on spontaneous motor activity. Thus, total locomotor activity and rearing activity were decreased. However, forward locomotion and peripheral locomotion were increased relative to the total horizontal activity. Furthermore, (3) 5-HTP accumulation, after inhibition of cerebral decarboxylase, was dose dependently decreased by both compounds in the ventral striatum and in the prefrontal cortex. There was a statistically significant decrease in DOPA accumulation in the ventral striatum after administration of a high dose of flesinoxan (3.2 mg kg-1), and a tendency for 8-OH-DPAT to produce the same effect. The efficacy of the compounds to affect male rat sexual behavior, spontaneous motor activity in the open-field and forebrain 5-HT synthesis was approximately the same, whereas flesinoxan was about an order of magnitude less potent than 8-OH-DPAT.
Ahlenius
S
S
Department of Neuropharmacology, Astra Research Centre AB, Södertälje, Sweden.
Larsson
K
K
Wijkström
A
A
D006916:5-Hydroxytryptophan / Q000378:metabolism; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000096:biosynthesis; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D016548:Prosencephalon / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D015306:Biogenic Monoamines; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C056895:flesinoxan; D004295:Dihydroxyphenylalanine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine; D006916:5-Hydroxytryptophan; D002262:Carboxy-Lyases