Modulation of the behavioral effects of chlordiazepoxide by methylxanthines and analogs of adenosine in squirrel monkeys

Abstract

The effects of chlordiazepoxide (CDAP) on suppressed behavior of squirrel monkeys were determined alone and in combination with selected methylxanthines (caffeine, theophylline, 8-phenyltheophylline, theobromine, 3-isobutyl-1-methylxanthine) and analogs of adenosine (L-PIA, N6-cyclohexyladenosine, NECA). Monkeys responded under a fixed-interval schedule of food presentation in which responding was suppressed by a concurrent fixed-ratio schedule of response-produced electric shock. Dose-effect curves were determined by administering cumulative doses i.v. during timeout periods that preceded sequential components of the schedule. When administered alone, CDAP produced dose-related increases in the rate of suppressed responding at doses up to 17.8 mg/kg and decreased responding at a higher dose of 32.0 mg/kg. Under the same conditions, the methylxanthines usually had only small effects on responding over the range of doses studied, whereas L-PIA and NECA usually decreased responding in a dose-related manner. After presession treatment with intermediate doses of caffeine, 8-phenyltheophylline or 3-isobutyl-1-methylxanthine, the increases is suppressed responding produced by CDAP often were larger than those produced by CDAP alone. In contrast, after presession treatment with low doses of L-PIA, NECA or N6-cyclohexyladenosine the increases in suppressed responding normally produced by CDAP were either reduced or eliminated. Although L-PIA, NECA and N6-cyclohexyladenosine attenuated the rate-increasing effects of CDAP, there was no indication that they produced an overall rightward shift in the CDAP dose-effect curve, suggesting that the adenosine analogs did not act simply as competitive antagonists of CDAP.(ABSTRACT TRUNCATED AT 250 WORDS)