Peter G. Henke

Hippocampal pathway to the amygdala and stress ulcer development

The objective of the first study was to localize the reported aggravation of stress ulcers found after large bilateral hippocampal lesions in rats. Lesions in the ventral hippocampus produced a similar increase in the severity of gastric erosions after cold-restraint, as was seen after large bilateral lesions. Dorsal hippocampal damage produced no differential effects. In the second experiment, high-frequency electrical stimulation of the ventral CA1 region of the hippocampus, a procedure known to induce long-term potentiation, increased the evoked potentials in the lateral central nucleus of the amygdala, and in adjacent parts of the lateral and basolateral nuclei. The increase in the efficacy of synaptic transmission in this pathway attenuated stress ulcer development. It was concluded that the ventral hippocampus is part of a coping system, and a strengthening of synaptic connections with the central amygdala increases the coping ability of rats under stress conditions.

The bed nucleus of the stria terminalis and immobilization-stress: Unit activity, escape behaviour, and gastric pathology in rats

Multiple unit-activity in the bed nucleus of the stria terminalis was increased or decreased, relative to baselines, during physical restraint in rats. Changes in unit-activity were also obtained by presenting an auditory stimulus that had been paired with the immobilization treatment. The animals escaped from that stimulus in behavioural tests, and bilateral lesions in the bed nucleus reduced the latencies of escape responses. The lesion also increased the severity of restraint-induced mucosal erosions. The latter effect was most pronounced when the damage was in the lateral portion of the bed nucleus. It was concluded that the bed nucleus of the stria terminalis is part of a coping system which responds when the organism is placed in a stressful situation.

The central amygdala and immobilization stress-induced gastric pathology in rats: neurotensin and dopamine

Bilateral microinjections of neurotensin (3, 10 and 30 micrograms) into the central amygdala had a dose-related attenuating effect on cold-restraint gastric ulcers in rats. Similar inhibitory effects were also observed with intra-amygdalar dopamine (3, 10 and 30 micrograms). Pretreatment with 6-hydroxydopamine (10 micrograms) or haloperidol (1 mg/kg), however, reversed the ulcer attenuating effect of neurotensin. The results indicate that the central amygdala is important in the mediation of the cytoprotective effects of neurotensin and dopamine.

The centromedial amygdala and gastric pathology in rats.

Abstract Bipolar electrical stimulation of the medial amygdala, primarily the central nucleus, produced gastric ulcers and hemorrhages in rats. Prior lesions of the ventral amygdalofugal pathway prevented the pathology, whereas lesions in the stria terminalis did not. Neuroanatomical circuits which may mediate these effects are described.

Lesions in the amygdala and the frustration effect

Abstract Responding in a double runway following the omission of reinforcement in the first goal box was investigated in rats with lesions in the amygdala. Analysis of runway speeds indicated that bilateral lesions in the amygdala prevented the occurrence of the frustration effect in the second alley and produced decreased vigor of performance in the first alley. Results were discussed in terms of frustration and changes in motivation.

Facilitation and inhibition of gastric pathology after lesions in the amygdala of rats

Abstract Bilateral lesions in the dorsomedial amygdala attenuated the effects of physical restraint on stomach pathology in rats. Posterolateral lesions increased the incidence and severity of gastric ulcers and hemorrhages. Combined lesions in these two amygdaloid areas also attenuated the restraint-induced pathology. It was concluded that the dorsomedial amygdala is excitatory, whereas the posterolateral area is inhibitory during restraint stress.

Opiate mechanisms in the central amygdala and gastric stress pathology in rats

Bilateral microinjections of the opiate antagonist naloxone (0.1, 1.0 and 10.0 micrograms) into the central nucleus of the amygdala (CEA) produced a significant potentiation of cold restraint-induced gastric pathology in rats. The opiate agonist, beta-endorphin (0.1, 1.0 and 10.0 micrograms), on the other hand, inhibited stress ulcer formation in a dose-related manner. Stress ulcer-attenuating effects were also seen with intra-CEA injections of the enkephalin analogs [D-Ala2,D-Leu5]enkephalin (10.0 micrograms) and [D-Ala2]Met-enkephalinamide (10.0 micrograms). Pretreatment of rats with naloxone (1.0 microgram) completely antagonized and even reversed the gastric cytoprotective effects of beta-endorphin (1.0 and 10.0 micrograms). The results indicate that the CEA is important in the gastric cytomodulatory effects of endogenous opiates during stressful experiences.

The Amygdala Emotions and Gut Functions

Studies are reviewed that indicate that the amygdala, and its temporal lobe pathways connecting it with entorhinal cortex and hippocampus, modulates the effects of stressful conditions on the development of gastric pathology. The amygdala integrates aversive stimulus conditions with the defensive behaviors and visceral reactions seen under such circumstances. The transmitter mechanisms for these effects include dopamine, γ-aminobutyric acid, thyrotropin-releasing hormone, neurotensin, enkephalins, and endorphins. Recording data also show that distinct neural “signatures” in this temporal lobe region correlate with the vulnerability to stressful experiences. The efficacy of synaptic transmission, as represented by potentiation or suppression of recorded neuronal responses, is an indication of coping adjustments, ie, habituation or behavioral helplessness. Glutamate receptors in this brain region, activated byN-methyl-d-aspartate, are implicated in these behavioral strategies. It is proposed that the neurophysiology of these limbic system structures produces individual differences in stress ulcer severity.

Recent studies of the central nucleus of the amygdala and stress ulcers

Studies are reviewed which indicate that the multiple-unit activity of the central nucleus of the amygdala differentiates stress-susceptible from stress-resistant rats, highly emotional from less emotional animals, and genetically-selected Roman High-Avoidance and Low-Avoidance rats. Kindling of this region increases the susceptibility to stress ulcer formation. Dopamine, neurotensin, and the endogenous opiates in the central nucleus are cytoprotective, whereas thyrotropin-releasing hormone aggravates the stress pathology. It is suggested that the amygdala codes the stressfulness of aversive inputs, the central nucleus being the point of output to areas controlling visceral responses to such information.

Kindling in the amygdala and susceptibility to stress ulcers

Kindling in the centromedial amygdala facilitated the subsequent development of restraint-induced stomach ulcers in rats. It was suggested that the neuronal hyperexcitability produced by the kindling procedure led to an increased susceptibility to gastric pathology in response to stress.