Disruption of FR-40 by 5-HT agonists. II. Effects of chronic phenelzine or isocarboxazid.
Effects of chronic treatment with the monoamine oxidase inhibitors phenelzine and isocarboxazid on disruption of FR-40 operant responses by 5-HT agonists have been studied. Three groups of rats that were trained in the FR-40 operant schedule showed marked disruption by 0.1 mg/kg IP lysergic acid diethylamide (LSD), 2 mg/kg IP quipazine (Q), 0.05 mg/kg SC 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT), and 1 mg/kg SC (m-trifluoromethyl-phenyl)piperazine (TFMPP), administered twice weekly in random order. Subsequently, one group received daily IP injection of phenelzine (5 and 10 mg/kg), the second group received 5 mg/kg IP of isocarboxazid, and the third group received vehicle (0.5% methyl cellulose) for 24 days (Period 1 and Period 2). For these periods and 12 days after discontinuing the MAOI treatments (Washout Period), test doses of 5-HT agonists were evaluated for their effects to decrease reinforcements (R) and increase pauses (P). No change in sensitivity to the LSD, Q and TFMPP effects on FR-40 behavior was observed in the vehicle-treated group. However, an attenuated effect of 8-OHDPAT was found in this group. In phenelzine- and isocarboxazid-treated rats the disruption of FR-40 responses by LSD and 8-OHDPAT were significantly reduced during Period 1, Period 2 and Washout Period. A significantly less effect on disruption in FR-40 responses by quipazine and TFMPP during Period 2 and the Washout Period was also seen. Since MAO inhibitors appear to down-regulate both 5-HT1 and 5-HT2 binding sites in brain, the attenuated effects of the 5-HT agonists were anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)
Shukla
R
R
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.
Goudreau
J
J
Mackenzie-Taylor
D
D
Rech
R H
RH
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D007520:Isocarboxazid / Q000494:pharmacology*; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010624:Phenelzine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects
D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D007520:Isocarboxazid; D010624:Phenelzine