title: The neurotensin-1 receptor agonist PD149163 inhibits conditioned avoidance responding without producing catalepsy in rats.
abstract: Agonists for neurotensin (NT)-1 receptors have produced antipsychotic-like effects in many animals, including reversal of prepulse inhibition deficits and psychostimulant-induced increases in spontaneous activity. The present study sought to provide a basic assessment of the putative antipsychotic effects of PD149163 in rats using a two way conditioned avoidance response task, which is highly validated for screening antipsychotic drugs, and an inclined grid assessment, which is used to assess extrapyramidal side effect liability. PD149163 (0.0625-8.0 mg/kg) significantly suppressed conditioned avoidance responding (CAR) following administration of a 1.0 or 8.0 mg/kg dose. PD149163 failed to significantly increase catalepsy scores. The typical antipsychotic drug haloperidol (0.01-1.0 mg/kg) significantly suppressed CAR at a 0.1, 0.3, and 1.0 mg/kg dose, and a significant increase in catalepsy scores was found at the 1.0 mg/kg dose. The atypical antipsychotic drug clozapine (2.5-10.0 mg/kg) also produced a significant inhibition of CAR, which occurred following administration of a 10.0 mg/kg dose. Clozapine failed to significantly increase catalepsy scores. Finally, D-amphetamine (1.0 mg/kg), serving as a negative control, failed to suppress CAR or increase catalepsy scores. These data further suggest that PD149163 may have atypical antipsychotic-like properties.
authors.affiliation: Psychology Department, Northern Michigan University, 1401 Presque Isle Ave., Marquette, Michigan, USA.
authors.forename: Elizabeth N
authors.initials: EN
authors.lastname: Holly
authors.forename: Bree
authors.initials: B
authors.lastname: Ebrecht
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Prus
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000633:toxicity; D001362:Avoidance Learning / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced*; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000633:toxicity; D003024:Clozapine / Q000494:pharmacology / Q000633:toxicity; D003214:Conditioning, Classical / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000819:agonists*
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; C117269:PD 149163; D018028:Receptors, Neurotensin; D009496:Neurotensin; D003024:Clozapine; D006220:Haloperidol; D003913:Dextroamphetamine