Corticotropin-releasing factor mediates the suppressing but not the facilitating effects of footshock on progressive-ratio cocaine self-administration.
Published: 2004
Language: eng
Number of pages: 224
Description: Stress contributes to drug addiction, and footshock has been used to study effects of stress on aspects of cocaine-motivated behaviour. However, the effects of acute footshock on the efficacy of cocaine reinforcement have not previously been studied. Corticotropin-releasing factor (CRF) is a neuropeptide known to mediate stress responses. CRF is also important for the effects of stress on aspects of cocaine-motivated behaviour, and for some of the effects of cocaine itself. These findings suggest that CRF could mediate alterations to the efficacy of cocaine reinforcement caused by footshock. Progressive-ratio cocaine self-administration was employed to examine the acute motivational consequences of footshock, and to test the hypothesis that brain CRF mediates these effects.Initial experiments examined behavioural changes produced by intermittent, non-contingent footshock applied to rats during self-administration sessions. Results showed that footshock altered break points for iv cocaine in a manner that depended on footshock intensity (0--2 mA) and duration (0--4.5 s): increases in intensity produced asymptotic increases in break point; increases in duration produced biphasic, inverted-U shaped effects on break point. Footshock also increased inactive lever responding and reinforcement rate. In contrast with the effects on cocaine reinforcement, footshock did not alter break points for sucrose.Together, these findings indicate that intermittent, non-contingent footshock can both facilitate and suppress ongoing cocaine-motivated behaviour, depending on the duration of footshock stimuli applied. CRF was implicated in the suppressing but not the facilitating effects of footshock on progressive-ratio cocaine self-administration.The role of CRF was tested using in vivo microdialysis to measure changes in nucleus accumbens neurochemistry following intracerebroventricular CRF infusions. Results indicated that CRF dose-dependently enhanced dopamine metabolites. In separate experiments the motivational consequences of CRF were tested directly, using either cocaine or sucrose reinforcement. The self-administration results showed that CRF (10 mug) attenuated break points for iv cocaine, but did not alter break points for sucrose. A final experiment tested the effects of intracerebroventricular infusions of alpha-helical CRF9--41  a non-selective CRF antagonist, on footshock-induced changes to progressive-ratio cocaine self-administration. The antagonist selectively reversed the descending portion of the inverted-U shaped effects of footshock on break points for cocaine.
Notes: Adviser: Franco J. Vaccarino.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-05, Section: B, page: 2683.