The applicant suggests that pain experience includes: (1) the sensory- discriminative dimension that signals the location, intensity and physical properties of a noxious stimulus and evokes rapid responses designed to prevent potential or future injury; (2) the affective-motivational dimension that ascribes to a noxious stimulus the affective-motivational dimension that ascribes to a noxious stimulus the percept of unpleasantness that motivates behaviors such as avoidance and recuperation; and (3) a cognitive-evaluative dimension that induces an appraisal of the meanings and consequences associated with painful sensations and injury. The current application is a second revision of a renewal after a FIRST award to the investigator. The focus of this application is the affective- motivational dimension of the pain experience with vocalization after discharges (VADs; vocalizations of the rat that exceed the application of the noxious experience; e.g. tailshock) as a model for this dimension. In previous studies by the investigator and other investigators, the investigator has concluded that VADs are elicited from a reciprocal rhinencephalic-diencephalic circuit which includes the vPAG/DR, nucleus parafascicularis, amygdala, habenula, and nucleus accumbens. The general hypothesis is that morphine, acting within the vPAG/DR, attenuate VADs by activating serotonergic neurons which project to the re=levant limbic areas; serotonergic neurons, in turn, activate enkephalinergic neurons, which contribute to the suppression of VADs. The proposed studies are designed (1) to examine the contribution of each of these brain areas to the elicitation of VADs and to the ability of vPAG/DR morphine to attenuate VADs; 92) to test the hypothesis that serotonergic neurons contact enkephalinergic neurons in each of the limbic areas; and (3) examine the hypothesis that morphine-induced attenuation of VADs requires the cooperation of each of the brain areas (e.g. removal of even one of the areas will reduce the effectiveness of morphine). The overall strategy is to examine the ability of the 5-HT antagonist methysergide and the opioid antagonist naloxone to antagonize the effects of morphine in the vPAG/DR. Each site will be examined in combination with morphine in the vPAG/DR and each site will be examined for the combination of methysergide and naloxone to test hypothesis (2) above The five anatomical sites will then be examined in pairs to test hypothesis (3) above. Each brain area will be subjected to electrical stimulation and chemical (NMDA) stimulation to test the hypothesis that activation of this area elicits VAD-like responses and each brain area will be damaged to test the hypothesis that removal of this area reduces tailshock elicited VADs.
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