Methamphetamine self-administration reduces alcohol consumption and preference in alcohol-preferring P rats

Subclinical levels of polysubstance use are a prevalent and understudied phenomenon. Alcohol is a substance commonly co-used with other substances of other drug classes. These studies sought to determine the consumption effects of combining alcohol drinking and methamphetamine (MA) self-administration. Male alcohol-preferring P rats had continuous access to a two-bottle alcohol drinking procedure in the home cage. Control rats remained alcohol naïve. Rats were also surgically implanted with intra-jugular catheters and trained to self-administer saline (control) or MA in daily 2-hour sessions. We first measured the acquisition and maintenance of MA intake in alcohol-consuming or control rats. MA intake was initially enhanced by alcohol consumption on a fixed ratio 1 schedule of reinforcement, but this effect did not prevail as the difficulty of the schedule (FR5 and progressive ratio) was increased. We next measured both alcohol consumption and preference before, during and after MA (or saline) self-administration. MA self-administration significantly reduced alcohol intake and preference ratios, a robust effect that persisted across several experimental variations. Interestingly, alcohol consumption rebounded following the cessation of MA self-administration. The effects of MA self-administration were specific to alcohol intake because it did not alter total fluid consumption or consumption of sucrose. MA self-administration did not impact blood-alcohol concentrations or alcohol-induced loss of righting reflex suggesting no effect of MA intake on the alcohol metabolism or sensitivity. Together, the results suggest that MA intake disrupts alcohol consumption and preferences but not the reverse in alcohol-preferring P rats.