F0 morphine self-administration

Sires were allowed to lever press for intravenous morphine (daily 3-hr sessions, 0.75 mg/kg morphine/59 μl saline, infused over 5 s) for 60 consecutive days (duration of rodent spermatogenesis) on a fixed ratio 1 (FR1) schedule of reinforcement, where one lever press resulted in a single infusion of morphine. Age-matched control rats received saline over the same time period. We and others have previously used this model [^{32, 33}]. Twenty-four hours after the last of the 60-day morphine self-administration session, sires were pair-housed with drug-naïve dams for up to 5 days to copulate. Both groups of sires continued to self-administer morphine (or saline) during the mating period to avoid withdrawal-mediated anxiety and stress as a confounding factor [^34–36]. At PND 21, we weaned offspring derived from morphine-experienced sires (morphine-sired) and saline controls (saline-sired) and pair-housed them with same-sex littermates. For each of the four groups (male saline-sired, male morphine-sired, female saline-sired, female morphine-sired) 1–2 adult (post-natal day 60 – 120) rats were randomly selected for behavioral and molecular analyses (Figure 1A).

A. F0 males self-administered either morphine (0.75 mg/kg/infusion) or saline for 60 days consecutively. On day 61, sires were paired with drug-naïve dams for breeding for up to 5 days. Following breeding, dams were separated from sires, and F1 progeny were born. B. Paternal morphine consumption did not alter the acquisition of morphine self-administration in adult female rats (from 8 saline-exposed sires and 10 morphine-exposed sires) at the 0.25mg/kg dose. C. Under the progressive schedule of reinforcement, saline-sired (from 8 sires) and morphine-sired (from 10 sires) female rats took similar amounts of morphine infusions. D. At the 0.75mg/kg dose, morphine self-administration was intact in female rats (from 8 saline-exposed sires and 6 morphine-exposed sires). E. There was no difference between saline-sired (from 8 sires) and morphine-sired (from 6 sires) female rats when they were switched to a progressive ratio schedule. F. In contrast to female progeny, paternal morphine exposure significantly enhanced morphine self-administration at the low dose in morphine-sired adult male rats (from 8 saline-exposed sires and 8 morphine-exposed sired). G. In line with these results, morphine-sired (from 8 sires) rats took significantly more infusions of morphine compared to saline-sired rats (from 8 sires) under a progressive ratio schedule. H. There was no difference in morphine infusions between saline-sired (from 5 sires) and morphine-sired male rats (from 6 sires) at the 0.75 mg/kg dose. I. Paternal morphine consumption did not alter morphine self-administration at the higher dose in male rats (from 5 saline-exposed sires and 6 morphine-exposed sires) under a progressive ratio schedule of reinforcement. Data are expressed as the mean ± S.E.M. *p < 0.05.