Impact of Age on Heroin Intravenous Self-Administration in Wistar Rats

Background: Evidence suggests steeper accelerating opioid-related overdose, and non-medical use rates, in middle aged men in recent years compared with younger cohorts. Little is known about whether this is driven by age-related differences in the effects of opioids compared with socio-cultural factors driving non-medical consumption. Rodent models can be useful for dissociating biological from psychosocial factors, however, only minimal evidence exists on the effects of opioids in middle-age rats. Objective: To determine if the anti-nociceptive and rewarding effects of opioids differ between adult and middle-age rats. Methods: Female and male Wistar rats were obtained in early adulthood and examined across 4 to 11 months of age for nociceptive responses to heroin (0-1.56 mg/kg, s.c.) using a warm-water tail withdrawal assay. Subgroups (N=8 per group) were initiated on intravenous self-administration (IVSA) of heroin at either 5 months or 12 months of age. Results: Anti-nociceptive effects of heroin did not differ across age. Female rats that initiated IVSA in early adulthood or middle-age obtained significantly more infusions of heroin than male rats of the same age during acquisition, and in dose-substitution under a FR1 schedule. Male, but not female, rats that initiated IVSA in middle age self-administered less heroin then rats that initiated in early adulthood; this was observed in acquisition and in dose-substitution. Discussion: This study shows that opioid reward is diminished in middle aged male rats. It also found that middle age rats can be used effectively to model opioid-related outcomes, including drug seeking using the IVSA procedure.