The objective of this research proposal is to identify and characterize brain systems involved in opite reinforcement. The relationship of these systems to those involved in other rewards, especially psychomotor stimulant reward, is also examined. The methodological focus of this project is on drug microinjetion techniques. The central line of study involves self-administration of morphine directly into brain tissue. Other studies determine the effects of drug microinjections on various behaviors such as brain stimulation reward and intravenous drug self-administration. Considerable evidence suggests tht opiates and psychomotor stimulants can activate the same reward system. This project should determine if additional neural systems are involved in opiate reward. One such system might be that responsible for physical dependence on opiates. Many investigators believe physical dependence to be a major factor in opiate addiction. While recent work has shown that opiates can be rewarding from an action on brain systems not involved in physical dependence, the relief of withdrawal distress may provide an additional motivation to ingest opiates. This research project will examine the ability of this negative reinforcement process to maintain behavior, and the efficacy of positive and negative reinforcement processes in the maintenance of opiate addiction will be directly compared.
Other specific aims of this project include the characterization of morphine self administration into the ventral tegmental area, the continuation of anatomical mapping for other brain sites where morphine microinjections are rewarding, a determination of the effect of rewarding ventral tegmental morphine on heroin and cocaine intravenous self-administration, and the identification of opiate-induced effects that are anatomically dissociated from their rewarding actions. The successful characterization of brain systems subserving opiate reinforcement will not only contribute to a basic understanding of drug addiction but may also provide the foundation for developing potential analgesics devoid of high abuse liability.
| Pudiak, Cindy M; KuoLee, Rhonda; Bozarth, Michael A (2014) Tolerance to cocaine in brain stimulation reward following continuous cocaine infusions. Pharmacol Biochem Behav 122:246-52 |
| Pudiak, Cindy M; Bozarth, Michael A (2013) Effect of post-trial L-NAME administration on cocaine sensitization. Int J Neurosci 123:663-9 |
| Bozarth, M A (1994) Physical dependence produced by central morphine infusions: an anatomical mapping study. Neurosci Biobehav Rev 18:373-83 |
| Bozarth, M A; Pudiak, C M; Morris, M (1994) Nitric oxide synthesis inhibition does not affect brain stimulation reward. Pharmacol Biochem Behav 48:487-90 |
| Pudiak, C M; Bozarth, M A (1994) Cocaine fatalities increased by restraint stress. Life Sci 55:PL379-82 |
| Pudiak, C M; Bozarth, M A (1993) L-NAME and MK-801 attenuate sensitization to the locomotor-stimulating effect of cocaine. Life Sci 53:1517-24 |
