A stimulus-control account of regulated drug intake in rats.
BACKGROUND
Patterns of drug self-administration are often highly regular, with a consistent pause after each self-injection. This pausing might occur because the animal has learned that additional injections are not reinforcing once the drug effect has reached a certain level, possibly due to the reinforcement system reaching full capacity. Thus, interoceptive effects of the drug might function as a discriminative stimulus, signaling when additional drug will be reinforcing and when it will not.


OBJECTIVE
This hypothetical stimulus control aspect of drug self-administration was emulated using a schedule of food reinforcement.


METHODS
Rats' nose-poke responses produced food only when a cue light was present. No drug was administered at any time. However, the state of the light stimulus was determined by calculating what the whole-body drug level would have been if each response in the session had produced a drug injection. The light was only presented while this virtual drug level was below a specific threshold. A range of doses of cocaine and remifentanil were emulated using parameters based on previous self-administration experiments.


RESULTS
Response patterns were highly regular, dose-dependent, and remarkably similar to actual drug self-administration.


CONCLUSIONS
This similarity suggests that the emulation schedule may provide a reasonable model of the contingencies inherent in drug reinforcement. Thus, these results support a stimulus control account of regulated drug intake in which rats learn to discriminate when the level of drug effect has fallen to a point where another self-injection will be reinforcing.
Panlilio
Leigh V
LV
National Institute on Drug Abuse, NIH/DHHS, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov
Thorndike
Eric B
EB
Schindler
Charles W
CW
D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage; D003216:Conditioning, Operant; D003463:Cues; D004193:Discrimination Learning; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D008027:Light; D008297:Male; D010880:Piperidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D012201:Reward; D012646:Self Administration
D000701:Analgesics, Opioid; D018765:Dopamine Uptake Inhibitors; D010880:Piperidines; D003042:Cocaine; D000077208:Remifentanil