Blockade of dopamine receptors explains the lack of 5-HT stereotypy on treatment with the putative 5-HT1A agonist LY165163.
The putative serotonin (5-HT)1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluormethylphenyl) piperazine (LY165163, PAPP) induces hyperphagia and hypothermia in rats, but unlike other 5-HT agonists, does not induce 5-HT stereotypy even at high doses (10 mg/kg sc). LY165163 (1 mg/kg) increased striatal DOPA accumulation in animals treated with the aromatic amino acid decarboxylase inhibitor 3-hydroxy-benzylhydrazine (NSD 1015) (100 mg/kg ip). This increase was also found when the drug was given to animals pretreated with parachlorophenylalanine (pCPA) (150 mg/kg ip daily for 3 days). LY165163 (2 and 4 mg/kg sc) inhibited stereotyped behaviour induced by the dopamine (DA) agonist apomorphine (2 mg/kg sc). LY165163 (2, 4, 10 mg/kg sc) also inhibited stereotyped components of the 5-HT syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 5 mg/kg ip) which previous studies (e.g. Andrews et al. 1982) suggested to require DA (head weaving, reciprocal forepaw treading). Thus, while other 5-HT1A agonists such as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) cause stereotypy, this does not occur with LY165163, probably because the drug blocks DA receptors.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D010134:Fenclonine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013239:Stereotyped Behavior / Q000187:drug effects*
D010879:Piperazines; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; C044643:LY 165163; D001058:Apomorphine; D010134:Fenclonine; D004298:Dopamine