Arunabha Ray

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.

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.

Central dopamine systems and gastric stress pathology in rats

Acute treatments with haloperidol (1 mg/kg), clozapine (10 mg/kg) and metoclopramide (10 mg/kg) significantly facilitated cold-restraint-induced gastric ulcer formation in rats. In addition, haloperidol and clozapine also produced gastric mucosal erosions in non-stressed rats. Bilateral lesions of the ventral tegmental area (VTA) and substantia nigra also aggravated stress ulcerogenesis--VTA lesions also being effective in inducing gastric ulcers in non-stressed rats. Long-term treatment with dopaminergic blockers showed variable effects. Clozapine potentiated the gastric stress pathology, whereas no significant facilitation was observed with haloperidol or metoclopramide. In addition, withdrawal from haloperidol did not influence the gastric ulcer formation when compared to controls. The role of central dopaminergic involvement in gastric stress pathology is discussed in light of the present results.

Effects of intra-amygdalar dopamine agonists and antagonists on gastric stress lesions in rats

Microinjections of dopamine (DA, 3 and 30 micrograms) or its agonist apomorphine (3 micrograms) into the central amygdala (CEA) attenuated cold restraint (3 h at 4 degrees C)-induced gastric ulcer formation in rats. Pretreatment with DA antagonists, haloperidol and metoclopramide (both i.p. and intra-amygdalar) reversed the stress ulcer attenuating effect of DA. It is suggested that the CEA is one of the central sites for this DA cytoprotection and that D2 receptors are possibly involved in this effect.

Interactions of thyrotropin-releasing hormone (TRH) with neurotensin and dopamine in the central nucleus of the amygdala during stress ulcer formation in rats

Bilateral microinjections of thyrotropin-releasing hormone (TRH; 1, 3 and 10 micrograms) into the central nucleus of the amygdala produced a dose-related aggravation of cold restraint-induced gastric ulcers in rats. TRH (10 micrograms) also induced gastric erosions in non-stressed animals. Pretreatment with atropine methyl nitrate attenuated the TRH-induced ulcers in both stress and non-stress situations. TRH (10 micrograms) also antagonized the gastric cytoprotection of intra-amygdalar neurotensin (10 micrograms) and was ineffective in altering the stress ulcer-attenuating effects of dopamine (10 micrograms). Pretreatment with i.p. clozapine, however, prevented the inhibitory effects of dopamine on the TRH-induced aggravation of the gastric stress pathology. The results suggest an interaction of TRH, neurotensin and dopamine in the central amygdalar nucleus during stress, and indicate peripheral cholinergic pathways in the mediation of the ulcerogenic effects of TRH.

Noradrenergic mechanisms in the central amygdalar nucleus and gastric stress ulcer formation in rats

Microinjections of noradrenaline (NA, 0.3, 3.0 and 30.0 micrograms) into the central amygdalar nucleus (CEA) produced dose-related attenuations of cold restraint (3 h at 4 degrees C) induced gastric ulcer formation in rats. On the other hand, stress ulcer aggravating effects were seen with beta-adrenoceptor antagonist, propranolol (10 micrograms) but not with the alpha-adrenoceptor antagonist, prazosin (1 and 10 micrograms). Moderate enhancements of gastric stress lesions were also seen with the NA release inhibitor clonidine (1 microgram) and the neurotoxin DSP-4 (25 micrograms). Further, pretreatment of rats with intra-amygdalar (i.am.) propranolol but not prazosin, antagonized and reversed the gastric cytoprotective effects of NA. The results indicate that beta-adrenoceptor-mediated NAergic mechanisms at the level of the CEA are important for the maintenance of gastric mucosal integrity during immobilization stress.

The GABA/benzodiazepine receptor complex in the central amygdalar nucleus and stress ulcers in rats.

The effects of bilateral microinjections of chlordiazepoxide and GABA into the central amygdalar nucleus on gastric ulcer formation induced by cold-restraint were examined in chronically implanted Wistar rats. Higher doses of chlordiazepoxide (20 and 30 micrograms/amygdala) significantly reduced stress ulcer development, whereas a lower dose (2.5 micrograms) produced a nonsignificant increase in ulcer severity. A similar dose/response pattern was observed following GABA administration. The benzodiazepine receptor antagonist Ro15-1788, applied to the amygdala, abolished the protective effects of both chlordiazepoxide and GABA. In addition, when Ro15-1788 (10 micrograms) was injected into the amygdala by itself, it aggravated the gastric stress pathology. However, a lower dose (5 micrograms) had an attenuating effect, opposite to the pattern of effects produced by chlordiazepoxide and GABA. The role of the amygdalar GABA-benzodiazepine receptor complex in stressful conditions is discussed.

Effects of intra-amygdalar thyrotropin releasing hormone (TRH) and its antagonism by atropine and benzodiazepines during stress ulcer formation in rats

Bilateral intra-amygdalar (i/am) microinjections of TRH (1 and 10 micrograms) and physostigmine (10 micrograms) into the central nucleus (CEA) aggravated cold restraint stress (3 hr at 4 degrees C) induced gastric ulcer formation in rats, whereas atropine (1, 5 and 10 micrograms) attenuated this phenomenon. Similar stress ulcer reducing effects were seen with chlordiazepoxide (CDP, 10 mg/kg, IP) and midazolam (1, 3 and 10 micrograms, i/am). Pretreatment of rats with atropine or CDP antagonized the ulcerogenic effects of both TRH and physostigmine. Further, when administered intra-CEA, midazolam neutralized the effects of TRH in a dose-related manner. These results are discussed in light of TRH-acetylcholine-benzodiazepine/GABA interactions within the amygdaloid complex during stress ulcer formation.

The effects of buspirone, a selective anxiolytic, on stress ulcer formation in rats ☆

The effects of buspirone hydrochloride were investigated on the formation of cold-immobilization gastric stress ulcers. Low doses significantly attenuated, while higher doses greatly potentiated gastric stress pathology. The dopamine antagonist haloperidol, and the agonist apomorphine respectively, reversed the buspirone effects. The role of dopamine in the expression of buspirones effects is discussed, although other transmitter systems may mediate some of the actions of buspirone.