The 2-deoxyglucose method was used to compare regional brain activities of unrestrained wild Norway rats engaged in fear-based defensive behavior (n = 8), and that of solitary controls (n = 8). After infusion with 100 micrograms/kg of (14C)-deoxyglucose via jugular catheters, experimental rats spent the 45-min uptake period in flight, boxing, and defensive attack to painless threat stimuli. Coronal sections of brains were exposed to X-ray film, and the resultant global maps of regional brain activity for the two groups were quantitated by high-resolution fiber optic densitometry at 86 cerebral points and analyzed statistically by computer. Significant group differences in regional brain glucose uptake were found at 16 loci. The considerable agreement between these structures and those previously identified in the literature as involved in defensive behavior provides evidence for the potential of this method of investigation of brain correlates of specific behavioral patterns.

Small lesions in the most posterior portion of the globus pallidus and adjacent internal capsule virtually eliminated fear or defensive reactions in wild Norway rats. Flight to an approaching experimenter, startle reactions to dorsal and vibrissae contacts, defensive attack to a conspecific and reactions to handling by human experimenters were grossly reduced following surgery and for a period of 30 days thereafter. After tail shock, however, some defensive behaviors reappeared. This pattern of behavior changes suggests a striking similarity between effects of the present small lesions and the “amygdala-lesion syndrome” of reduced defensiveness to nonpainful stimuli. It is also similar but not identical to the reduced defensiveness which follows damage to the midbrain central gray, with the difference between the two lesions suggesting that more complex fear-eliciting stimuli are processed at the higher site.

Wild-trapped Rattus norvegicus show a consistent pattern of fear and defensive behavior to nonpainful stimuli such as an approaching experimenter, an anesthetized conspecific, or tactile stimulation of the back and vibrassae, as well as to painful stimuli. This reactivity to a range of stimuli, and the different behaviors by which such fear or defensiveness may be expressed, including flight, freezing, vocalization, the jump-attack, and specific biting patterns, make wild rats very appropriate subjects for the analysis of brain mechanisms underlying fear. Lesions of the mesencephalic central gray dramatically lowered these defensive reactions to both painful and nonpainful threat stimuli, reducing or eliminating each of the defensive reactions measured. The subjects showed no evidence of significant motor impairment or disturbance of primary sensory mechanisms. Because these experimental lesions involved considerable damage to the superior colliculi, a second study used wild rats with damage only to the colliculi. These animals displayed some deficits in visually guided behavior and in reactivity to certain tactile stimuli, but most of their fear reactions were intact. These findings suggest that the mesencephalic central gray, traditionally regarded as involved in reactivity to pain, may be one component of a mechanism underlying fear and defensive behaviors to nonpainful as well as noxious stimuli.

Rats with anterior septal lesions showed a pattern of consistent enhancement of defensive behaviors normally elicited by threatening conspecifics, with no enhancement of attack or general reactivity. Further division of this group indicated that damage to sites anterior and ventral to the septal area, sites previously implicated in the "septal syndrome," produces maximal effect on these behaviors. When amygdala lesions are combined with septal damage this enhanced defensive responding is almost completely eliminated. These results were interpreted as indicating that the septal syndrome represents hyperdefensiveness to conspecific threat stimuli rather than aggression or increased general reactivity, and that amygdaloid mechanisms are also involved in the regulation of conspecific defensive behaviors.

Rats with hippocampal damage show a marked deficit in a variety of experiments requiring prolonged movement arrest. It is suggested that this inability of the hippocampal rat to “hold still” may be central in our understanding of the hippocampal syndrome.