Association between initial morphine intake and body weight change, acoustic startle reflex and drug seeking in rats

Rationale Although chronic use of opiates can induce physical dependence and addiction, individual differences contributing to these symptoms are largely unknown. Objectives Using intravenous morphine self-administration (MSA), we investigated whether individual differences in drug intake are associated with weight change, acoustic startle reflex (ASR), pre-pulse inhibition (PPI), and drug seeking during spontaneous withdrawal. Methods Male Sprague-Dawley rats self-administered morphine (0.5 mg/kg/infusion) or saline for 3 weeks (4-6 h/day, 5 days/week) and drug intake and body weight were monitored daily. The ASR and the PPI (baseline, 1 day and 1 week) and drug seeking (1 week) were measured during spontaneous withdrawal. Results Morphine animals did not gain weight (101%+0.69), while the control animals did (115 %+1.06) after 3 weeks of self-administration. The ASR and the PPI were not significantly different between morphine and saline animals in 1-day or 1-week withdrawal. However, individual differences in initial (first 10 min), but not total (4-6 h), morphine intake of the daily sessions were positively correlated with weight change (r=0.437, p=0.037) and drug seeking (r=0.424, p=0.035) while inversely correlated with the ASR (r=-0.544, p=0.005) in 1-week withdrawal from chronic morphine. Conclusions A subgroup of animals that self-administered a larger amount of morphine at the beginning of the daily sessions exhibited subsequent weight gain, reduced ASR, and enhanced drug seeking in morphine withdrawal. Thus, individual differences in initial morphine intake may reveal a novel behavioral phenotype in opioid addiction.