Considerable evidence suggests that opiates and psychomotor stimulants activate the same reward system. At least part of the reinforcing effects of opiates involve the activation of the ventral tegmental dopamine system, and psychomotor stimulant reinforcement is mediated primarily through this system. This research project should determine if another neural system is also involved in opiate reward. Many investigators believe that physical dependence is a major factor in opiate addiction. While previous work has shown that opiates can be reinforcing from an action on brain systems not involved in physical dependence, the relief of withdrawal distress may provide an additional motivation to self- administer opiates. This series of experiments will examine the ability of this potential negative reinforcement process to maintain drug-taking behavior, and it will provide the basis for evaluating the efficacy of positive and negative reinforcement processes in the maintenance of opiate addiction. Intravenous opiate administration distributes drug throughout the brain, and many different effects are produced by concurrent opiate actions in different brain regions. Research using direct drug application into brain tissue has shown a neuroanatomical dissociation of some opiate effects, such as positive reinforcement, physical dependence, and thermoregulatory changes. By using intracranial microinjections, neural systems mediating positive reinforcement can be activated (viz, from ventral tegmental opiate application) without the development of physical dependence, and physical dependence can be produced (viz, from periventricular gray opiate application) without activating neural systems involved in positive reinforcement. Thus, selective activation of these two opiate-receptor fields can evoke mechanisms subserving either positive or negative reinforcement processes. A major objective of this project is to determine if animals made physically dependent on morphine infused directly into the periventricular gray area will learn to intracranially self-administer morphine into that brain region. If so, this would provide the first substantial evidence that a negative reinforcement process can maintain opiate drug-taking behavior, and it would provide an experimental preparation for further tests of the importance of such negative reinforcement mechanisms. Others studies examine the development of physical dependence during intravenous opiate self-administration, and they explore the role of physical dependence in intravenous drug reinforcement. This series of studies will evaluate the potential role of negative reinforcement processes in opiate self-administration. The successful establishment of periventricular gray morphine self-administration in physically dependent laboratory rats provides a method for assessing the importance of negative reinforcement mechanisms in drug-taking behavior. This experimental procedure would permit-for the first time-a direct comparison of the relative reinforcing strength of appetitive and aversive motivational mechanisms in the maintenance of opiate intake.
| 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; 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 |
| Bozarth, M A (1994) Physical dependence produced by central morphine infusions: an anatomical mapping study. Neurosci Biobehav Rev 18:373-83 |
| 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 |
