title: A stimulus-control account of dysregulated drug intake.
abstract: Drug self-administration typically occurs in a regular temporal pattern, with a consistent pause following each injection. We have proposed that this patterning results from differential reinforcement of post-injection pausing. In this view, even when every response produces an injection, some injections are not reinforcing because they occur when the level of drug effect is already maximal; consequently, drug reinforcement occurs on an intermittent schedule, and the interoceptive drug effect functions as a cue, indicating when another injection will be reinforcing. Previously, we emulated this situation with rats by using food reinforcement; each response was recorded as delivering a "virtual" injection, and a visual cue tracked the virtual drug level to indicate availability of reinforcement. This emulation schedule produced response patterns strikingly similar to actual drug self-administration. In the present study, the emulation schedule was modified to determine whether reinforcement of pausing is sufficient to produce these patterns, or whether a cue is necessary. Without a cue, response patterns were irregular and virtual drug intake was escalated. These results suggest that a failure of interoceptive cues to control pausing might contribute to the dysregulated drug intake that is associated with addiction.
authors.affiliation: Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, NIH/DHHS, 251 Bayview Blvd, Baltimore, MD 21224, USA. lpanlili@intra.nida.nih.gov
authors.forename: Leigh V
authors.initials: LV
authors.lastname: Panlilio
authors.forename: Eric B
authors.initials: EB
authors.lastname: Thorndike
authors.forename: Charles W
authors.initials: CW
authors.lastname: Schindler
mesh_terms: D000818:Animals; D008297:Male; D009042:Motivation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration