Blockade of conditioned avoidance responding by trazodone, etoperidone, and MCPP.
Phenylpiperazines, such as meta-chlorophenylpiperazine (MCPP) a serotonin agonist, have recently been reported to block conditioned avoidance responding (CAR) in the rat, which is an indication of possible antipsychotic utility. Since MCPP is a major metabolite of both antidepressant drugs trazodone (TZ) and etoperidone (ET), both were examined for activity in blocking CAR in a single-trial lever press task in Fisher 344 rats. Both TZ and ET produced dose-related falls in CAR with ED50 values (95% confidence limits) of 13.3 (9.6, 18.5) and 10.4 (8.5, 13.2) mg/kg IP, respectively. In contrast, MCPP had an ED50 value of 2.5 (1.8, 3.6) mg/kg IP TZ, ET, and MCPP were also examined for the production of catalepsy and the blockade of amphetamine-induced stereotypy to determine whether each was acting to block CAR via a dopaminergic mechanism of action. None, however, was found highly active. On the other hand, the serotonin receptor blocker metergoline (1.0 mg/kg IP) significantly reduced the CAR block produced by each, suggesting a serotonergic mechanism of action. Since TZ and ET are both less potent than MCPP, the data also suggest TZ and ET may block CAR via formation of MCPP.
Martin
G E
GE
Department of Biological Research, McNeil Pharmaceutical, Spring House, PA.
Mathiasen
J R
JR
Kesslick
J M
JM
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000187:drug effects; D014196:Trazodone / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000928:Antidepressive Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D008711:Metergoline; C013528:etoperidone; C015068:1-(3-chlorophenyl)piperazine; D014196:Trazodone