Opioids, cocaine, and food change runtime distribution in a rat runway procedure

The nature of the relationship between the dose of a drug of abuse and its reinforcing effect has come under close scrutiny. It is currently debated if the steep ascending part of the biphasic dose-response curve typically obtained in multiple-dosing lever-press-based operant conditioning procedures represents a satiety-driven, all-or-none response or if the response is gradual and tightly adjusted to the various doses of the reinforcer.

Dose-response relationships of drug reinforcers (remifentanil, alfentanil, morphine, cocaine) as well as a physiological reinforcer, i.e. food (sweetened condensed milk) were investigated in a different operant conditioning paradigm, i.e. a runway procedure.

Administration of the mu opioid receptor agonists remifentanil (0.0032-0.1 mg/kg IV), alfentanil (0.032 mg/kg IV), morphine (0.032-1 mg/kg IV), the psychostimulant cocaine (0.001-0.1 mg/kg IV) or sweetened condensed milk (diluted 1:100-1:3 in water) was made contingent upon alley running for male Sprague-Dawley rats.

All drug reinforcers dose-dependently decreased runtimes and, more importantly, significantly increased the percentage of runs at a certain speed (> or =10 cm/s) from an average 29% to an average 71% (water versus milk, 22% versus 83%).

Both drug- and food reinforcers produced a discontinuous, qualitative change in the rats' operant behavior rather than a simple gradual increase along a continuum, an effect that could be seen clearly only after a histogram analysis of runtime distribution.