Neurochemical and behavioural evidence for an agonist action of 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163) at central 5-HT receptors.
1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163, PAPP) (1 mg/kg s.c.) significantly decreased 5-hydroxytryptophan (5-HTP) accumulation in cortex, hippocampus, striatum, septum, pons + medulla and midbrain and increased DOPA accumulation in the cortex and striatum following inhibition of aromatic amino acid decarboxylase with NSD 1015. LY 165163 increased food intake in non-food-deprived rats over 2, 4 and 24 h after administration. Depletion of brain 5-hydroxytryptamine (5-HT) by parachlorophenylalanine (pCPA) prevented the hyperphagic effect over 2 and 4 h after treatment with LY 165163 (1 mg/kg). Components of the postsynaptically mediated 5-HT behavioural syndrome were not detected at doses of LY 165163 between 1 and 10 mg/kg, although locomotion was increased at lower doses and the rats were inactive at the highest dose. Results in general indicate that LY 165163 is a centrally active agonist at 5-HT presynaptic receptors.
D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001679:Biogenic Amines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects*; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects
D001679:Biogenic Amines; D010879:Piperazines; D011985:Receptors, Serotonin; D004295:Dihydroxyphenylalanine; C044643:LY 165163; D006916:5-Hydroxytryptophan