Morphine: effects on positive and negative intracranial reinforcement thresholds
Marcus, Richard A.
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The mechanism of morphine analgesia is poorly understood. There is some anatomical, physiological, and behavioral evidence implicating the mesencephalic reticular formation in pain perception, and in morphine analgesia. The first part of this experiment was an attempt to determine, in rats, thresholds for escape from direct electrical stimulation of the reticular formation, and to determine the effects of morphine on these thresholds. Several investigators have hypothesized that the positive reinforcement systems in the brain may be involved in the production of the narcotic "high." It is also possible that these structures are related to the reinforcement-like aspects of narcotic addiction. The second part of this study was an attempt to determine positive reinforcement thresholds for direct electrical stimulation of the medial forebrain bundle (MFB), the major component of these reward pathways, and to determine the effects of morphine on these thresholds. Previous attempts to measure negative and positive reinforcement thresholds have, for the most part, employed variations of the classical method of limits. This method, however, suffers primarily from the fact that stimulus intensities are presented in a serial order. The method of constant stimuli has been found to be unreliable in addition to its theoretical shortcomings. The double staircase method, however, reduces, if not eliminates, the theoretical and practical problems of these other procedures, and was therefore used in the present study to measure intracranial reinforcement thresholds. Subjects were six male Fischer-derived albino rats. Three animals were implanted with electrodes in the reticular formation, and three with electrodes in the MFB. These electrodes were found to be negatively and positively reinforcing, respectively. The animals were then trained in the appropriate threshold determination task. Subjects were tested for several sessions until the change in threshold in response to saline injections was stable from session to session. The effects of various doses of morphine sulfate on these thresholds were then investigated. It was found that morphine increased the thresholds for escape from electrical stimulation of the reticular formation. These increases were dose-related, in that higher doses of the drug produced a greater increase in threshold. The results indicated that higher levels of stimulation were required to elicit escape responding after morphine than were required before drug administration, and therefore suggested that morphine depresses the excitability of the reticular formation in response to aversive stimulation. Thus, these results further implicate the reticular formation in the mediation of morphine analgesia. It was also found that morphine decreased the positive reinforcement thresholds for MFB stimulation. These decreases were dose-related in a U-shaped manner, that is, low to moderate doses decreased thresholds, while higher doses had no apparent effect on threshold. These results indicated that the animals were responding in order to receive levels of stimulation which were in fact lower than even pre-morphine detection levels, and therefore suggested that morphine increases the excitability of the positive reinforcement systems in the brain. It was concluded that this increase in excitability may be the neural mechanism involved in the production of the narcotic "high," and may also be related to the development of narcotic addiction.
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