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In nonstressed rats, subcutaneous administration of haloperidol (HAL) and large doses of diazepam (DZ) increased plasma corticosterone (CS). Hypothalamic norepinephrine (NE) was lowered significantly by desmethylimipramine (DMI), HAL and, to a lesser extent by DZ and phenobarbital (PHB). In rats pretreated with either DZ, DMI, HAL or PHB the restraint-induced rise of CS was diminished, DZ being most potent. CPZ had a variable effect, slightly increasing or decreasing the CS response. Pretreatment (16 hr) with pargyline (PA) did not affect the CS rise to stress. The reduction of hypothalamic NE evoked by restrain was attenuated by DZ, and to a lesser extent, by PHB and HAL. Restraint of PA-treated rats did not lower the PA-elevated hypothalamic NE. The stress-induced increase in hypothalamic dopamine was prevented by CPZ and, partially, by PHB. It is emphasized that the net plasma CS and brain catecholamine changes in response to stress are dependent on the drug-induced neuroendocrine feedback state prevalent immediately before commencement of the stress procedure.

Restraint causes an increase in plasma renin activity (PRA) which is not affected by pretreatment with dl-propranolol (1 mg/kg IP) or sotalol (15 mg/kg IP). These doses of β-adrenergic blocking agents are effective in suppressing the stimulation of PRA by isoproterenol. Large doses of dl-propranolol (10 mg/kg IP) and d-propranolol (5 mg/kg IP) attenuate the restraint-induced PRA increase. Adrenal demedullectomy does not affect the PRA response to restraint. Renal denervation blunts the PRA rise due to restraint, but not to direct stimulation by the β-adrenergic agonist, isoproterenol. It is concluded that the increase in PRA during restraint stress in rats is not solely dependent on an intact renal sympathetic innervation. A significant portion of this stress-induced PRA increase appears to involve a non-adrenergic mechanism.

In the chloralose-anaesthetized cat, stimulation of forelimb cutaneous afferent nerves evoked a response in the preganglionic splanchnic nerve, consisting of a short duration spinal reflex followed by a supraspinal component of longer duration. Diazepam (0·1–1·4 mg/kg, i.v.) markedly attenuated the supraspinal reflex but had a considerably lesser effect on the segmental response. On the other hand, diphenylhydantoin (10–40 mg/kg, i.v.) reduced predominantly the spinal component, whilst the supraspinal reflex was frequently enhanced after the initial dose of 10 mg/kg. This effect of diphenylhydantoin on the spinal reflex was direct, since it also occurred in the spinal cat. Phenobarbital (10–40 mg/kg, i.v.) was approximately equally potent in reducing both the spinal and supraspinal reflex. Visceromotor reflexes were markedly depressed by very small doses of diazephm (0·001 mg/kg, i.v.) and by larger doses of phenobarbital (10–20 mg/kg, i.v.). Diphenylhydantoin, although reducing this reflex, did not completely block it at the highest total dose tested (40 mg/kg, i.v.). The results indicate that the three CNS depressants differentially affect the spinal and supraspinal components of the somatosymphetic reflex. Furthermore, the three drugs also differ quantitatively from each other in depressing the spino-bulbo-spinal transmission of the viscerosomatic reflex.

Restraint stress of 30 min increases plasma CS and lowers hypothalamic NE. Restraints of longer durations are associated with an attenuation of these changes. Daily repetitive restraint enhances the CS response on the second day and progressively diminishes it on subsequent days. Whole brain NE increases on the first day and decreases on Day 2 to 5. The CS response to acute restraint is similar is similar in 5 different normotensive rat strains, but is enhanced in the genetically hypertensive SH rat, its normotensive backbreed WKY, and the DOCA hypertensive Sprague-Dawley rat. Comparison with other stressors (electric foot shock and novel environment) indicate that the responses to restraint are different at least in time course, if not qualitatively.