Behavioural effects of the alpha 2-adrenoceptor antagonists idazoxan and yohimbine in rats: comparisons with amphetamine.

Although yohimbine has long been known to increase arousal, reactivity and anxiety in animals and humans, little is known about the behavioural effects of more selective alpha 2-adrenoceptor antagonists such as idazoxan. In a recent experiment, however, it was found that in rats both yohimbine and idazoxan increased low rates of lever pressing, an effect also produced by amphetamine. The purpose of the present study was to investigate further the effects of yohimbine and idazoxan in comparison with those of d-amphetamine on the operant behaviour of rats. In rats trained to press a lever on a FI 60s schedule to obtain food both yohimbine and idazoxan increased response rates, although the effect of yohimbine was considerably greater than that of idazoxan. Lower doses of d-amphetamine had no consistent effect on overall rates of responding whereas a higher dose suppressed responding. Characteristically, d-amphetamine increased responding during early portions of the intervals and decreased responding during the final portions. Idazoxan and yohimbine tended to increase responding throughout the intervals except immediately after reinforcement. When idazoxan was administered in combination with prazosin FI response rates were markedly decreased. Administration of DSP4 did not alter the response rate-increasing effects of either yohimbine or idazoxan. In rats trained to discriminate d-amphetamine from saline both idazoxan and yohimbine gave rise to responding on the saline associated lever. Combination of idazoxan with d-amphetamine did not antagonise the amphetamine cue but produced substantial reductions in response rates, probably due to toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)