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

Abstract

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)

The CRF1 receptor antagonist antalarmin attenuates yohimbine-induced increases in operant alcohol self-administration and reinstatement of alcohol seeking in rats

“…In addition, the effect of yohimbine on locomotor activity has been inconsistent with studies showing either increases (Schroeder et al 2003) or decreases in locomotion (Chopin et al 1986;Delini-Stula et al 1979). Others have shown that within the dose range used here, yohimbine either increased (Sanger 1988;Sethy and Winter 1972), did not change (Hughes et al 1996), or decreased (Appel et al 1999;Munzar and Goldberg 1999) lever responding maintained by food.…”

Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats

“…For example, yohimbine was found to either increase (Schroeder et al 2003) or decrease (Delini-Stula et al 1979;Chopin et al 1986) locomotion. Also, within the dose range we used, yohimbine either increased (Sethy and Winter 1972;Sanger 1988), did not change (Hughes et al 1996), or decreased (Appel et al 1999;Munzar and Goldberg 1999) lever responding maintained by food. The findings that yohimbine had no effect on inactive lever responding (Figs 2, 3) further suggest that a potential effect of yohimbine on general activity cannot account for its effects on alcohol self-administration and reinstatement.…”

Neural Activation Profile Elicited by Cues Associated with the Anxiogenic Drug Yohimbine Differs from That Observed for Reward-Paired Cues

“…Instead of pairing an injection of a rewarding drug with a specific environment, an environment was paired with an injection of yohimbine, an anxiogenic a-2 adrenergic receptor antagonist. Yohimbine causes an increase in the firing of central nervous system noradrenergic neurons and, in humans, increases subjective reports of anxiety (Charney et al, 1983;Uhde et al, 1984;Sanger, 1988). Similarly, in animal studies, yohimbine has been shown in multiple paradigms to be apparently anxiogenic, causing conditioned place aversion, potentiated startle, decreased social interaction and decreased exploration (Davis et al, 1979;Pellow et al, 1985;Chopin et al, 1986;File, 1986;Bhattacharya et al, 1997).…”