Figure 4.

Effects of alpha-2 adrenoceptor agonists on stress-induced reinstatement in rats and stress-induced craving in humans. (a) Rat studies: Data are mean±SEM non-reinforced active lever presses after exposure to intermittent footshock or no shock immediately prior to the reinstatement tests in rats with a history of heroin, cocaine, speedball (a heroin-cocaine combination), or alcohol self-administration. The session duration was 3 h for heroin, cocaine, and speedball, and 1 h for alcohol. The intermittent footshock duration was 15 min for heroin, cocaine, and speedball, and 10 min for alcohol. Clonidine and lofexidine were injected 25–45 min before intermittent footshock exposure. (b) Human studies: Left side: Data are mean±SEM subjective craving responses assessed on an ordinal Likert scale in opiate users (maintained on naltrexone) or cocaine users who were pretreated with lofexidine or clonidine, respectively, or placebo and exposed to a guided imagery stress or no stress (neutral guided imagery) manipulation. Right side: days to first lapse in human subjects that received chronic placebo or clonidine in a clinical trial. Data were redrawn from Erb et al (2000), Highfield et al (2001), Jobes et al (2011), Kowalczyk et al (2014), Le et al (2005), Shaham et al (2000b), and Sinha et al (2007). *Different from the vehicle (0 dose) in the stress condition or different from the placebo condition, p<0.05.