Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

Norway rat pups were either handled (H) or undisturbed (nonhandled, NH) in the period between birth and weaning on Day 21. Following weaning, half of the animals in each group were housed socially (Soc), and half were housed in isolation (Isol). At 120-150 days of age, all animals were sacrificed, and the following regions were dissected and frozen at -70 degrees C until the time of assay: frontal cortex, hippocampus, hypothalamus, amygdala, septum, and pituitary. [3H]Dexamethasone (3H Dex) binding in each region was examined by an in vitro, cytosol, receptor assay. 3H Dex binding was significantly higher in the hippocampus of both H-Soc and H-Isol than in NH groups. In the frontal cortex, 3H Dex binding was higher in the H-Soc animals than in the H-Isol and NH-Isol animals. There were no significant handling or housing effects found in the amygdala, hypothalamus, septum, or pituitary. Thus, early postnatal handling appears to influence the development of the glucocorticoid receptor system in the hippocampus and frontal cortex. These results are discussed as providing a possible mechanism for some of the previously reported effects of early handling on the development of the pituitary-adrenal response to stress.

Hyperthermia in the rat from handling stress blocked by naltrexone injected into the preoptic-anterior hypothalamus.

Experimental handling and colonic temperature measurement have been shown to cause stress and induce a long-lasting rise in colonic temperature in the rat. This stress-induced hyperthermia was blocked by microinjection of the narcotic antagonist naltrexone into the preoptic-anterior hypothalamus (POAH) of the brain, but was not significantly affected by similar injections into areas of the brain above the POAH. Thus, the stress-induced hyperthermia may be caused by activation of the endogenous opioid mechanism in the POAH.

Enkephalinase inhibition antagonizes the increased susceptibility to seizure induced by REM sleep deprivation.

In order to elucidate the relationship between REM sleep and the enkephalinergic system, the effects of REM sleep deprivation (REMSD), stress and the enkephalinase inhibitor phosphoramidon on handling-induced convulsions were studied in mice. REMSD, stress and phosphoramidon (25-500 micrograms icv) increased the frequency of handling-induced convulsions (HIC) in normal mice. However, only in the last two groups were HIC antagonized by naloxone (1 mg/kg IP). In REMSD mice, phosphoramidon decreased the frequency of HIC, this effect being abolished by naloxone. The increase of neuronal excitability during REMSD is suggested to be associated with an insufficiency of the enkephalinergic system.

Effects of acute and chronic treatments with atenolol and propranolol on cardiovascular responses to handling stress in spontaneously hypertensive rats.

Although the mechanism of antihypertensive action of beta-adrenergic blocking drugs (beta-blockers) is not known, a theoretical advantage of cardioselective beta-blockers over nonselective ones has been proposed in the treatment of hypertension. To study this hypothesis, we examined cardiovascular responses to handling stress in spontaneously hypertensive (SHR) rats after a single (100 mg/kg) and multiple oral treatments (100 mg/kg per day for 17 d) with either atenolol or propranolol. Atenolol and propranolol markedly suppressed the tachycardia induced by handling stress after acute and chronic administration. Resting mean arterial pressure (MAP) was reduced by acute and chronic atenolol treatment, but not by propranolol. Stress-induced increase in MAP was significantly reduced by chronic treatment with propranolol, whereas no consistent effects were observed with atenolol. Acute treatment with guanethidine (30 mg/kg) markedly reduced the rise in MAP induced by stress. These results suggest that suppression of cardiac function by beta-blockers does not always attenuate the rise in MAP induced by stress, thus cardioselective beta-blockers might not confer any further reduction of the blood pressure increase due to sympatho-adrenal excitation. Inhibition of stress-induced MAP rise by propranolol could be mediated by a modulation of the catecholamine release.

Effects of drugs affecting the noradrenergic system on convulsions in the quaking mouse.

Handling-induced convulsions in the quaking mouse can be blocked by: phenobarbital, pentobarbital or phenytoin; postsynaptic alpha-adrenoceptor agonists (noradrenaline, phenylephrine, CRL 40028); presynaptic alpha-adrenoceptor blockers (yohimbine, mianserine); catecholamine liberating agent (amphetamine); noradrenaline reuptake inhibitors (cocaine, imipramine, desipramine). Moreover, the protective effect of yohimbine was antagonized by clonidine, prazosin or alpha-methylparatyrosine, and the protective effect of CRL 40028 was antagonized by prazosin but not by alpha-methyltyrosine. Drugs acting by other mechanisms (pilocarpine, atropine, trihexyphenidyl, (--)-5-HTP, methysergide, pimozide, clonidine, alpha-methyl DOPA, prazosin, isoprenaline, salbutamol) did not protect against convulsions. A slight protection was obtained with high doses of apomorphine and also with (+/-)-propranolol. This effect is probably not related to blockade of beta-adrenoceptors because the same effect was obtained with (+)propranolol. In young quaking mice, where susceptibility to convulsions is low, both postsynaptic alpha-adrenoceptor blockers and presynaptic alpha-adrenoceptor antagonist lowered the convulsive threshold. Thus, this seems to constitute an interesting model for the in vivo study of substances which affect the central alpha-adrenoceptors either pre- or postsynaptically.

Variations in brain and heart acetylcholine content in rat: cervical dislocation vs guillotine technique.

The stress induced in animals due to handling prior to sacrifice has been shown to produce changes in total acetylcholine (Ach) content of the brain and heart of adult rats. Two methods of killing the animals were compared viz. cervical dislocation and decapitation by a guillotine technique; the former method producing more handling stress than the latter. Ach levels were significantly lower both in brain and heart when the animals were killed by cervical dislocation.

Effect of handling on positive and negative contrast effects.

The effects of early handling on the exhibition of positive and negative contrast effects were investigated. Over two 4-day testing sessions, animals were given alternating 1-min access periods to 2 bottles containing either 32 or 4% sucrose solutions. Measures of lick rate and latency to switch bottles revealed that both handled and nonhandled animals exhibited contrast effects of equal magnitudes. The results did not support an emotional interpretation of contrast effects but were interpreted as support for the perceptual theory of this phenomenon.

Infantile stimulation induces brain lateralization in rats.

The hypothesis tested was that the effects of early experiences are asymmetrically distributed in the two brain hemispheres. Litters were either handled or not handled between birth and weaning, and the weanlings were reared in either laboratory cages or enriched environments between 21 and 50 days. When approximately 135 days old, animals within each of the four treatment groups had a right neocortical ablation, a left neocortical ablation, a sham operation, or no surgery. About 1 month later, all animals were given the open-field test for emotionality and exploratory behavior. Ablating either the right or left neocortex increased the activity scores of nonhandled controls, but there was no evidence of lateralization. However, the groups handled in infancy did show lateralization. Ablating the left brain did not significantly increase activity, but ablating the right brain caused extreme scores: handled rats without enrichment experience were the most active, and handled rats also placed into the enriched environment had near-zero scores in the open field.