Pharmacological investigations of a yohimbine–impulsivity interaction in rats

Abstract

Both impulsivity and stress are risk factors for substance abuse, but it is not clear how these two processes interact to alter susceptibility for the disorder. The aim of this project was to examine the pharmacology of a stress-impulsivity interaction in rats. To do so, we tested the effects of yohimbine on impulsive action and then assessed whether behavioural changes could be reduced by antagonists at different receptor subtypes. Male Long-Evans rats were injected with various doses of yohimbine (0-5.0 mg/kg) before testing in the response-inhibition task. In subsequent experiments, yohimbine (2.5 mg/kg) was injected following pretreatment with the following receptor antagonists: corticotropin-releasing factor receptor 1, antalarmin (0-20 mg/kg); glucocorticoid, mifepristone (0-30 mg/kg); noradrenergic (NA) α1, prazosin (0-2 mg/kg); NA α2, guanfacine (0-0.5 mg/kg); NA β2, propranolol (0.5-2.0 mg/kg); dopamine D1/5, SCH 39166 (0-0.0625 mg/kg); μ opioid, naloxone (0-2 mg/kg); or 5-HT2A, M100907 (0.005-0.05 mg/kg). In all experiments, impulsive action was measured as increased premature responding. Yohimbine dose dependently increased impulsive action, but the effect was not reversed by antagonist pretreatment. None of the drugs altered any other behavioural measure. We conclude that stress-impulsivity interactions are likely mediated by a synergy of multiple neurotransmitter systems.

Differences in trait impulsivity do not bias the response to pharmacological drug challenge in the rat five-choice serial reaction time task

“…Yohimbine reliably increases impulsivity in rats in a range of response-inhibition tasks (Mahoney et al 2016 ; Schippers et al 2016 ; Sun et al 2010 ), some of which are conceptually analogue to the human Continuous Performance Task, suggesting that a yohimbine challenge can be considered as a tool for translational studies. Our data are not only generally in line with these reports but also extend these findings by demonstrating that yohimbine-induced impulsivity is not affected by underlying trait impulsivity.…”

Noradrenergic Regulation of Two-Armed Bandit Performance

“…Finally, the increased noradrenergic tone caused by systemic yohimbine can lead to increased measures of impulsivity in a variety of tasks (Mahoney et al, 2016; Sun et al, 2010; Swann et al, 2005). While we found an increase in speed and decrease in accuracy under yohimbine, we did not find evidence of a correlation between decision time and accuracy, indicating that yohimbine did not necessarily cause an increase in impulsivity.…”

Increased motor impulsivity in a rat gambling task during chronic ropinirole treatment: potentiation by win-paired audiovisual cues

“…However, a recent study suggests that the increase in preference for uncertain rewards caused by pramipexole cannot be explained by the ability of this drug to blunt changes in phasic dopamine release (Pes et al 2017). Yohimbine, an α 2 adrenoceptor antagonist which results in disinhibition of noradrenergic neurons through blockade of autoreceptors, increases premature responding on the 5CSRT through noradrenergic mechanisms (Adams et al 2017b; but see also Mahoney et al 2016). Furthermore, it is well-documented that salient sensory stimuli potently activate phasic activity within the noradrenergic system (Aston-Jones and Cohen 2005;Usher et al 1999), such that the cued rGT may theoretically elicit greater noradrenergic activity.…”