The overall goal of the proposed project is to gain a better understanding of the neural mechanisms governing the regulation of affective defense behavior in the cat and to provide an effective model for evaluating potential therapeutic agents. In the regulation of affective defense behavior. Our basic thesis is that opioid peptides powerfully modulate affective defense behavior by interacting with receptors at sites in the brain which are critical for the expression and control of this behavior. These structures include components of the limbic forebrain -- the amygdala, bed nucleus of the stria terminals (BNST), and nucleus accumbens -- which are known to modulate affective defense behavior, and the midbrain periaqueductal gray (PAG), which is essential for the expression of this response. the rationale for this project is based upon the facts that: (1) these structures contain an abundance of opioid receptors, enkephalin positive cells and terminals; (2) these structures are fundamental to the organization of affective defense behavior; and (3) that pilot experiments demonstrate that peripheral administration of the opioid antagonist, naloxone, or, local infusion of a general, metenkephalin agonist into the limbic-midbrain significantly modulates the occurrence of affective defense reactions. Several hypotheses are to be tested. The first is that PAG elicited attack can be modulated by components of the limbic forebrain and PAG. The second hypothesis is that opioid peptides play a major modulatory role in affective defense behavior both within the PAG as well as elsewhere within the limbic-midbrain. This study will determine which opiate subtypes are effective in modulating affective defense behavior at rostral and caudal levels of the PAG and within the amygdala, BNST and nucleus accumbens. The third hypothesis states that the PAG receives significant inputs from the amygdala and related structures and comprises the principal brainstem structure for integration of autonomic and somatic motor components of the affective defense response. The methods employed for these tract tracing studies will include tritiated amino acid radioautography and PHA-L immunocytochemistry.
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| Bhatt, Suresh; Bhatt, Rekha; Zalcman, Steven S et al. (2008) Role of IL-1 beta and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat. Brain Behav Immun 22:224-33 |
