A choice procedure to assess the aversive effects of drugs in rodents.
The goal of this series of experiments was to develop an operant choice procedure to examine rapidly the punishing effects of intravenous drugs in rats. First, the cardiovascular effects of experimenter-administered intravenous histamine, a known aversive drug, were assessed to determine a biologically active dose range. Next, rats responded on each of two levers with concurrently available fixed-ratio 1 schedules of food reinforcement. Intravenous histamine was delivered along with food when responses were made on one of the options, and the lever on which both food and histamine were contingent was switched on a regular basis. A dose of 1.0 mg/kg/inj of histamine was effective in moving responding to the alternate lever, whereas saline, 0.1, or 0.3 mg/kg/inj of histamine were not. Histamine injections produced reliable selection of the alternate lever when they were presented on the same lever for three consecutive sessions, but not when they were switched between levers on each session. In addition, histamine produced greater selection of the alternate lever when it was presented with shorter intertrial interval durations. These findings indicate that, with appropriate parameters, the aversive effects of histamine and perhaps other drugs can be established rapidly using a concurrent choice procedure.
Podlesnik
Christopher A
CA
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, 1150 W Medical Center Dr., Ann Arbor, MI 48109-5632, USA. cpod@umich.edu
Jimenez-Gomez
Corina
C
Woods
James H
JH
D000339:Affect / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects*; D005502:Food; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects*; D017442:Histamine Agonists / Q000009:adverse effects; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D009483:Neuropsychological Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration / Q000523:psychology
D017442:Histamine Agonists; D006632:Histamine