Reinforcing effect of subcutaneous morphine in a modified Ettenberg runway

Alley running has been successfully used as an operant to demonstrate both the positive and negative reinforcing effect of intravenously administered drugs of abuse in a bona fide operant conditioning paradigm, the Ettenberg runway, in which confounding drug effects on motor performance and drug accumulation are avoided. While Ettenberg and colleagues focus on the intravenous route of drug administration, we tested the practicability of the subcutaneous route of administration in this runway paradigm in Sprague Dawley rats, using morphine as the investigated drug of abuse. We also modified the Ettenberg runway, most notably in that either food (sweetened condensed milk), no food, morphine, or saline was presented outside the runway in a separate cage. This made shaping, i.e., the initial presentation of a food reinforcer within the runway, necessary to establish responding. The manipulations necessary to administer subcutaneous (sc) injections were well tolerated by over 90% of the tested rats (n = 93). However, sc injections increased runtimes to the experimenter cutoff of 60 s within 20 once-daily sessions. Because of strong experimenter effects, all morphine doses or saline had to be adminstered blind. Under these experimenter-blind conditions, 0.1 and 1 mg/kg subcutaneous morphine proved to be reinforcing in that these doses significantly slowed down the gradual increase in runtimes imposed upon by the sc injection procedure. Thus, morphine can be demonstrated to be a positive reinforcer in a modified Ettenberg runway even when given subcutaneously. This effect, however, is eventually overcome by the negative reinforcing effect of subjecting the animals to sc injection procedure.