Heroin self-administration as a function of time of day in rats

Abstract

Drug addiction is a complex disease that is impacted by numerous factors. One such factor, time of day, influences drug intake, but there have been no investigations of how time of day affects the amount of drug taken and the development of addiction-like behavior. Previous data from our group show circadian disruption in rats given access to heroin during the light phase, which is important because circadian disruption, itself, can increase drug intake. Thus, the goal of this experiment was to determine how time of day of access affects heroin self-administration and the development of addiction-like behaviors including escalation of heroin intake, willingness to work for heroin on a progressive ratio schedule of reinforcement, seeking during extinction, incubation of seeking, and reinstatement of heroin-seeking behavior. Male Sprague Dawley rats were given the opportunity to self-administer heroin for 6h per trial during the second half of either the light or dark phase for 18 trials, including one progressive ratio challenge. Rats then underwent 14days of abstinence, with a 5-h extinction test occurring on both the first and the 14th days of abstinence. The second extinction test was followed by a heroin prime and 1h of reinstatement testing. On the following day, a subset of rats were tested in an additional extinction test where rats were tested either at the same time of the day as their previous self-administration sessions or during the opposite light/dark phase. Relative to Light Access rats, Dark Access rats took more heroin, exhibited more goal-directed behavior, exhibited more seeking during the dark phase, failed to extinguish seeking during the 5-h extinction test in the dark phase, and exhibited greater incubation of heroin seeking following abstinence. However, Dark Access rats did not escalate drug taking over trials, work harder for drug, or seek more during drug-induced reinstatement than Light Access rats. These results show that time of access to heroin affects overall heroin intake and seeking in extinction, but does not affect other addiction-like behaviors in rats.