Cholecystokinin B receptors in the periaqueductal gray potentiate defensive rage behavior elicited from the medial hypothalamus of the cat.

Defensive rage behavior is mediated over a descending pathway from the medial hypothalamus to the dorsolateral midbrain periaqueductal gray (PAG) where further integration of this response takes place. The present study sought to determine the roles of CCK-A and CCK-B receptor activation in the PAG in modulating defensive rage behavior. The 'hissing' component of the defensive rage response was used throughout the experiment as the measure of defensive rage behavior. The basic design of the experiment involved placement of monopolar electrodes into the medial hypothalamus from which defensive rage could be elicited and cannula electrodes into the dorsal PAG for purposes of identifying defensive rage sites in this region and for microinjections of CCK compounds into these sites at a later time. Microinjections of the selective CCK-B receptor antagonist, LY288513 (1.05, 4.2, 17.0 nmol/0.25 microliter), into the PAG suppressed the hissing response in a dose- and time-dependent manner. Microinjections of the CCK-B agonist, pentagastrin, (0.5 and 1.0 nmol/0.25 microliter) facilitated the occurrence of defensive rage behavior. Moreover, administration of LY288513 (17 nmol/0.25 microliter) 55 min prior to pentagastrin (1.0 nmol/0.25 microliter) delivery blocked the facilitatory effects of pentagastrin. Administration of the CCK-A antagonist, PD140548 (34 nmol/0.25 microliter), into the PAG failed to alter response latencies for defensive rage behavior. In contrast, microinjections of the CCK-B antagonist, LY288513 (4.2, 17.0 nmol/0.25 microliter), facilitated the occurrence of predatory attack behavior elicited from the lateral hypothalamus. This finding demonstrates the specificity of the effects of CCK-B receptor blockade upon hissing. A combination of immunocytochemical and retrograde tracing procedures using microinjections of Fluoro-Gold (8%, 6 microliters) into the PAG were employed to identify the possible loci of CCK neurons that project to the PAG. The data revealed that neurons labeled for both CCK and Fluoro-Gold were located in the dorsolateral aspect of the midbrain tegmentum, identifying this region as a source of CCK inputs to the PAG. Overall, the findings demonstrate that CCK-B receptors in the PAG potentiate defensive rage behavior and likely suppress predatory attack.