U50,488 Discrimination in C57BL/6J, DBA/2J and 129/SvImJ mice

Young adult, male C57BL/6J, DBA/2J, and 129/SvImJ mice were trained to make a nose‐poke response to interrupt a photocell beam and gain access to evaporated milk. During discrimination training, interruption of one of two photocells was reinforced under a tandem VI100 FR20 schedule of reinforcement following 3 mg/kg (C57BL/6J and DBA/2J) or 2 mg/kg (120/SvImJ) U50,488; interruption of the other photocell beam was reinforced under the same schedule following saline administration. On test days, milk was presented upon the interruption of either photocell under a tandem FI100 FR20 schedule of milk presentation. All drugs were administered by the sc route. Under training conditions, U50,488 produced >80% drug‐appropriate responding in all three strains, and a small decrease in the rate of responding. Under test conditions, U50,488 (0.3 – 5.6 mg/kg) produced saline‐appropriate responding at low doses and U50,488‐appropriate responding at doses of 1.8 mg/kg and higher. Pretreatment with 1 mg/kg naloxone blocked the U50,488‐appropriate responding and the rate decreasing effects of U50,488. Neither fentanyl (1 – 56 ug/kg) nor morphine (0.1 – 5.6 mg/kg) produced U50,488‐appropriate responding even at doses that suppressed rates of responding in the three strains. Naloxone (1 mg/kg) antagonized the rate decreasing effects of fentanyl and morphine in the three strains. These results suggest that the morphine stimulus in these mouse strains maybe predominantly mediated by the mu opioid receptor. This work was supported by NIDA grant #DA14196.