Drug abuse is a major health and social problem in today's society. For over three decades neuroscientists have studied intravenous drug self-administration behavior in animals not only to search for the underlying neurochemical mechanisms and potential future drugs or abuse, but also to understand the drug-rewarded behavior itself. Over the same time, rewarding intracranial self-stimulation has been studied as an animal model of euphoria, with a particular recent emphasis on quantitative or psychophysical measurement methods. Despite the obvious similarities, self-administration behavior has typically been regarded as different from self-stimulation behavior, principally because after moderate responding is established, drug self-administration behavior often increases after dose is reduced or partially blocked, whereas self-stimulation behavior decreases under the similar conditions. Recently, our laboratory and one in Canada have demonstrated that many aspects of self-administration behavior can be produced with electrical brain stimulation if it is delivered unconventionally in a waveform which emulates the presumed time course of drug action. In addition to general theoretical interest, this finding opens up the behavior of drug self-administration to quantitative modeling using brain stimulation psychophysics. The first experiment of this proposal will independently vary peak, duration, and growth characteristics of a drug-like waveform of brain stimulation and examine the effects on """"""""self-administration"""""""" behavior at a macro level (i.e. average response rate) and micro level (e.g. loading phase, response bursting). In actual drug self-administration, the above factors are inherently confounded when dose is altered. In later experiments, Dl/D2 receptor blockers will be applied, electrode site varied, and the findings compared to the first set of psychophysical results. Finally, quantitative studies will be conducted on the role of aversiveness in determining an """"""""optimal"""""""" level of stimulation (like a defended blood level of drug). Because this is a novel approach a short grant format has been selected. Future grant proposals will focus on the application of psychophysical methods to cocaine self-administration.
| Melnick, S M; Maldonado-Vlaar, C S; Stellar, J R et al. (2001) Effects of repeated GBR 12909 administration on brain stimulation reward. Eur J Pharmacol 419:199-205 |
