The ?2-adrenoceptor antagonists idazoxan and yohimbine increase rates of DRL responding in rats

Abstract

Previous studies have reported that antidepressant drugs exert specific effects on responding maintained by DRL schedules of reinforcement, giving rise to increased frequencies of reinforcement. In order to investigate whether the alpha 2-adrenoceptor antagonist idazoxan would produce similar effects, the actions of this compound were compared with those of yohimbine, imipramine, mianserin and d-amphetamine in rats trained to lever press for food reinforcement on a DRL 60-s schedule. Neither imipramine nor mianserin produced any effects on response rate or reinforcement frequency, except at the highest doses. In contrast, both idazoxan and yohimbine gave rise to dose-related increases in rates of responding and consequent decreases in reinforcement frequencies. Amphetamine also increased responding, but higher doses of this drug produced marked hyperactivity and stereotyped movements which were not observed after idazoxan and yohimbine. Although the present behavioural baseline was not sensitive to antidepressants, it demonstrated an unexpected activity of two alpha 2-adrenoceptor antagonists which deserves further investigation.

Differential modulation of efficiency in a food-rewarded "differential reinforcement of low-rate" 72-s schedule in rats by norepinephrine and serotonin reuptake inhibitors

“…The present data corroborate numerous studies employing a water reward Seiden 1980a, 1980b;O'Donnell and Seiden 1983;Howard and Pollard 1984;Olivier et al 1993), and two studies employing a food reward (Sanger 1988;Van Hest et al 1992), in demonstrating that the DRL 72-s procedure is responsive to the tricyclic imipramine. The increase of efficiency elicited by the "atypical" agent mianserin is similarly in line with work with water-rewarded DRL 72-s models (O'Donnell and Seiden 1983;Marek et al 1989b;Hand et al 1991;Jackson et al 1995;Jones et al 1998) and is of significance since mianserin was inactive in a DRL 60-s model with food reward (Sanger 1988).…”

“…The increase of efficiency elicited by the "atypical" agent mianserin is similarly in line with work with water-rewarded DRL 72-s models (O'Donnell and Seiden 1983;Marek et al 1989b;Hand et al 1991;Jackson et al 1995;Jones et al 1998) and is of significance since mianserin was inactive in a DRL 60-s model with food reward (Sanger 1988). …”

“…Third, the great majority of previous investigations of the DRL 72-s procedure have utilised water reward. To expand the data base available for this procedure (Sanger 1988;Britton and Koob 1989;Van Hest et al 1992;Bright et al 1997;Jones et al 1998), and in analogy to certain delayed reinforcement models (Bizot et al 1988(Bizot et al , 1999Al-Ruwaitea et al 1999), we employed a food reward. Fourth, inasmuch as monoamine reuptake inhibitors modulate food intake and motor behaviour (Bray and Greenway 1999;Carek and Dickerson 1999;Rowland et al 2000;Millan et al 2001a), in independent experiments, the influence of drugs on these parameters was examined.…”

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

“…Sethy and Winter (1972) reported that low doses of yohimbine produced small increases in rates of punished and unpunished responding in rats maintained by a variable-interval schedule and Katz (1984) found that yohimbine increased FI response rates in pigeons. More recently, the present author (Sanger 1988) found that both idazoxan and yohimbine increased the very low rates of responding maintained by a DRL schedule. In that experiment, as in the present one, yohimbine produced a greater effect than idazoxan.…”

“…Preliminary clinical results have suggested that idazoxan may have some utility in the treatment of depression (Crossley 1984) but there have been relatively few reports describing the behavioural effects of this compound in laboratory animals. In one recent study (Sanger 1988), the effects of idazoxan and yohimbine were compared with those of imipramine, mianserin and d-amphetamine using rats trained to respond on a differential reinforcement of low rate (DRL) schedule of food reinforcement. The c~2-adrenoceptor antagonists did not produce antidepressant-like effects but rather gave rise to increased rates of responding, as did d-amphetamine.…”