Prazosin Prevents Increased Anxiety Behavior That Occurs in Response to Stress During Alcohol Deprivations

Abstract

Aims: Stress-induced anxiety is a risk factor for relapse to alcohol drinking. The aim of this study was to test the hypothesis that the central nervous system (CNS)-active α 1 -adrenergic receptor antagonist, prazosin, would block the stress-induced increase in anxiety that occurs during alcohol deprivations. Methods: Selectively bred male alcohol-preferring (P) rats were given three cycles of 5 days of ad libitum voluntary alcohol drinking interrupted by 2 days of alcohol deprivation, with or without 1 h of restraint stress 4 h after the start of each of the first two alcohol deprivation cycles. Prazosin (1.0 or 1.5 mg/kg, IP) or vehicle was administered before each restraint stress. Anxiety-like behavior during alcohol deprivation following the third 5-day cycle of alcohol drinking (7 days after the most recent restraint stress ± prazosin treatment) was measured by performance in an elevated plus-maze and in social approach/avoidance testing. Results: Rats that received constant alcohol access, or alcohol access and deprivations without stress or prazosin treatments in the first two alcohol deprivations did not exhibit augmented anxiety-like behavior during the third deprivation. In contrast, rats that had been stressed during the first two alcohol deprivations exhibited increased anxiety-like behavior (compared with control rats) in both anxiety tests during the third deprivation. Prazosin given before stresses in the first two cycles of alcohol withdrawal prevented increased anxiety-like behavior during the third alcohol deprivation. Conclusion: Prazosin treatment before stresses experienced during alcohol deprivations may prevent the increased anxiety during subsequent deprivation/abstinence that is a risk factor for relapse to alcohol drinking. Short summary: Administration of prazosin before stresses during repetitive alcohol deprivations in male alcohol-preferring (P) rats prevents increased anxiety during a subsequent deprivation without further prazosin treatment. Prazosin treatment during repeated alcohol deprivations may prevent the increased anxiety that is a risk factor for relapse to alcohol drinking.

Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder

“…Guanfacine and prazosin, but not propranolol, dramatically reduced MB. These results are consistent with the literature implicating a1AR activation in behavioral reactivity to novelty (Stone et al 2006), maintenance of generalized arousal (Broese et al 2012;Porter-Stransky et al 2019;Stone et al 2003), and stress-induced anxiety (Rasmussen et al 2016;Skelly et al 2014).…”

Higher pretreatment blood pressure is associated with greater alcohol drinking reduction in alcohol-dependent individuals treated with doxazosin

“…However, it is important to keep in mind that the sample studied here did not have other comorbidities like PTSD and/or anxiety disorders, so it was unlikely to observe a medication effect on these secondary outcomes. It is possible that, in patients with such comorbidities, α 1 receptor blockade may prevent the increase in anxiety due to alcohol deprivation, which in turn may represent a mechanism for relapse prevention, as recently observed in alcohol-preferring (P) rats (Rasmussen et al, 2016). …”

Effects of chronic prazosin, an alpha-1 adrenergic antagonist, on anxiety-like behavior and cortisol levels in a chronic unpredictable stress model in zebrafish (Danio rerio)

“…In addition, prazosin-treated groups had lower levels of cortisol than non-stressed, vehicle-treated subjects, although this decrease did not reach statistical significance. Prazosin treatment may function to generally prevent reactions to stress (Rasmussen, Kincaid & Froehlich, 2017); thus, further studies should also determine whether preventative prazosin treatment is effective at blocking any chronic or acute stress effects on anxiety-like behavior or neuroendocrine dysfunction. These studies would help clarify whether prazosin would be clinically efficacious, not by normalizing the effects of trauma or stress, but by preventing any responses to further triggering stimuli that may elicit PTSD symptomology.…”