BASAL AMYGDALOID FACILITATION OF MIDBRAIN PERIAQUEDUCTAL GRAY ELICITED DEFENSIVE RAGE BEHAVIOR IN THE CAT IS MEDIATED THROUGH NMDA RECEPTOR

The present study tested the hypotheses that: (1) defensive rage behavior elicited from the midbrain periaqueductal gray (PAG) in the cat is facilitated from the basal complex of amygdala; and (2) such facilitation from this region of amygdala is mediated via a pathway in which excitatory amino acids acting upon NMDA receptors within the PAG are utilized as a neurotransmitter. In the first phase of this study, cannula electrodes were implanted into PAG sites for the elicitation of defensive rage behavior as well as for drug delivery. Then, a second monopolar electrode was implanted into the basal nucleus of amygdala from which facilitation of defensive rage could be obtained. As a result of dual stimulation of the basal amygdala and PAG, response latencies for defensive rage were significantly lowered relative to PAG stimulation alone (P < 0.01). In the second phase of this experiment, 3 doses of a selective NMDA receptor antagonist, AP-7 (0.1, 0.5, 1.0 mg/kg), were peripherally (i.p.) administered in 5 animals. The results indicated a significant decrease in the facilitatory effects of amygdaloid stimulation in a dose and time dependent manner (P < 0.001). In the third phase, AP-7 was administered intracerebrally into PAG defensive rage sites in doses of 0.2 and 2.0 nmol. It was noted that intracerebral microinjections of AP-7 at the higher dose (2.0 nmol) also significantly suppressed the facilitatory effects of amygdaloid stimulation (P < 0.01); however, these effects were somewhat less potent then those observed following peripheral drug administration. A fourth phase of the study was conducted at the completion of the pharmacological experiments. Here, retrograde axonal tracing of amygdaloid neurons projecting to the PAG following Fluoro-Gold microinjections placed in defensive rage sites was coupled with an immunocytochemical analysis of the distribution of excitatory amino acid positive neurons present within the basal amygdala. The findings revealed the presence of high concentrations of glutamate and aspartate positive cells located mainly within the basal and lateral nuclei of amygdala, while retrogradely labeled cells within the amygdala were confined to its basal complex, central nucleus and anterior amygdaloid area. More significantly, dense quantities of cells double labeled with both Fluoro-Gold and excitatory amino acids were identified within the basal complex of amygdala. Collectively, these findings support the view that neurons arising from the basal complex of amygdala serve to facilitate defensive rage behavior, in part, by virtue of their projections to the PAG and that this phenomenon is mediated by a mechanism utilizing excitatory amino acids that act through NMDA receptors.