Sex differences among adult and adolescent rats in METH-induced CTA with extended CS-US trace intervals

Recent data show a dramatic increase in stimulant use in the past five years. Amidst this rise, methamphetamine (METH) use is contributing to increases in stimulant overdose deaths. Understanding factors that contribute to stimulant use are critical to the current public health landscape. It is well known that age and sex modulate the acceptability of drugs. Research suggests the balance of appetitive and aversive characteristics of drugs can influence future and continued use. The present set of studies examined METH-induced conditioned taste avoidance (CTA) to assess how age and sex impact learning when the trace interval between the unconditioned and conditioned stimulus is extended up to several hours. In Experiment 1, adult rats underwent METH CTA with 0-to-6-h trace intervals across three days followed by a two-bottle saccharin preference test. In Experiment 2, adolescent rats were assigned to METH or lithium chloride CTA groups at intervals of up to 4 h. In Experiment 3, the trace interval was set at 4 h and METH doses varied (0-10 mg/kg). Results indicate adults' CTA learning is systematically weaker as trace intervals increase and females show weaker aversion learning than males. Moreover, adolescents display generally weak aversions to METH, particularly at longer trace intervals. The greatest sex differences are found at the 4-h trace interval. These data contribute to studies examining sex and age as factors in drug use vulnerability. The results indicate female adolescents are likely more vulnerable than other groups to METH.