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.