Alterations in ethanol seeking and self-administration following yohimbine in selectively bred alcohol-preferring (P) and high alcohol drinking (HAD-2) rats

Evidence suggests that stress increases alcohol drinking and promotes relapse in humans. Animal models that assess related behaviors include the sipper tube ethanol self-administration and the stress-induced reinstatement paradigms. While selectively bred for the same high-ethanol-drinking behavior, alcohol-preferring P rats appear to show greater sensitivity to ethanol reinforcement than high-alcohol-drinking HAD rats. The present experiment tested the effects of the pharmacological stressor, yohimbine, on the motivation to seek and consume ethanol implementing a combined sipper tube/reinstatement model using male P and HAD-2 rats. Following training to self-administer ethanol using the sipper tube procedure, rats were tested for the effects of yohimbine (0.625–2.5 mg/kg) on ethanol drinking. Subsequently, rats were tested for the effects of 1.25 mg/kg yohimbine on reinstatement of ethanol seeking. Yohimbine (0.625 and 1.25 mg/kg) increased ethanol self-administration, and the latter dose also decreased latency to complete the response requirement. Yohimbine elicited reinstatement of ethanol seeking in both lines. HAD-2 rats drank more ethanol, but showed similar responding on the ethanol-associated lever compared to P rats. These findings extend both the reinstatement and sipper tube models and justify further exploration of this unique combined paradigm. Despite prior evidence suggesting that P rats are more motivated to seek and consume ethanol, differences in these behaviors between P and HAD-2 rats were not systematic in the present experiment. Further investigation may elucidate whether either selected line may be more sensitive than other selectively bred or outbred rats to stress-related changes in ethanol's reinforcing effects.

► Yohimbine increased ethanol self-administration and reinstated ethanol seeking.
► P and HAD-2 do not differ in the effects of yohimbine on ethanol reinforcement.
► The sipper tube model can be modified to test for reinstatement.