The Journal of Pharmacology and Experimental Therapeutics
Circadian rhythms in the response to ethanol were investigated in male, Swiss-Webster mice. Significant circadian variations were observed in increased and decreased spontaneous locomotor activity induced by ethanol (2 or 4 mg/g i.p., respectively) and in the hypothermic response to ethanol with the greatest effect generally occurring during the dark phase of the 12 hr:12 hr. light-dark cycle when the normal activity of the animals was highest. Ethanol was also more lethal during the dark phases as compared to the light phase.
Our experiments demonstrate that morphine and haloperidol produce two distinct and contrasting behavioral states, which can be thought of as exaggerated, isolated, and simplified forms of organized adaptive behavioral states functioning as components of normal motivated behavior. Haloperidol catalepsy constitutes an organized state in which tonic reactions subserving the maintenance of stable static equilibrium prevail, at the expense of phasic locomotor reactions.
Hippocampal electrical activity has been studied in 12 unanaesthetized, unrestrained rabbits during hypnosis and spontaneous activity in the experimental cage, before and among hypnosis trials. Quantitative analyses showed that rhythmic slow activity (RSA) occurred during exploratory movements (mean frequency 7.2 Hz) and also during spontaneous immobility, but a lower percentage and frequency (6.5 Hz).
General pharmacological studies on T-1982 produced the following results. On central nervous system, subcutaneous injection of T-1982 at dose of 2,000 mg/kg hastened the onset of pentetrazole-induced tonic extensor in mice. T-1982 had no effect on spontaneous motor activity, pentobarbital hypnosis, body temperature or EEG in mice or rabbits, and also did not show motor incoordinate, anticonvulsive or analgesic activity in mice at intravenous doses of 250--1,000 mg/kg or subcutaneous doses of 500--2,000 mg/kg.
Archives Internationales De Pharmacodynamie Et De Thérapie
Metamizol (sodium N-(1,5-dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-N-methylamino-methylsulphonate; Dipyrone) a non-narcotic analgesic was tested for hypnotic potentiating effect. Metamizol potentiated the hypnosis induced by pentobarbital, barbital and chloral hydrate. This effect was dose-dependent and was inversely proportional to the duration of the analgesic pretreatment. An augmented hypothermia and competition at drug metabolizing sites seem to be the mechanisms involved in the observed effect.
The activity of 33 neurons of pontomesencephalic dorsolateral periaqueductal gray matter (PAG), not triggered by motor or sensory stimuli, has been recorded during tonic immobility (animal hypnosis) and after morphine injection (5 mg/kg IV). Several parameters of neural activity were chronically studied, including: frequency, variability and pattern of discharge. Tonic immobility affected the frequency and the variability of the firing rate of the majority of neurons. Morphine decreased frequency and increased variability of 73.3% of the neurons.
The ability of adenosine to modify the CNS effects of acute and chronic ethanol was studied by using theophylline, an adenosine antagonist, and dipyridamole, a blocker of adenosine reuptake. We also studied the binding characteristics of adenosine using crude membranes of whole brain. Theophylline pretreatment prior to acute ethanol administration markedly reduced the duration of ethanol-induced sleep and similarly decreased the intensity and duration of motor incoordination.
Cesium chloride (CsCl) at several dose levels (1.25-20.0 mEq/kg IP) was administered acutely to albino mice whose behavior was compared with that in corresponding saline controls. Motor activity decreased and Straub tail occurred in a dose-related manner. Signs of autonomic disturbance, diarrhea, and salivation were seen with toxic doses. Subchronic administration of CsCl (5.0 mEq/kg/day IP for 7 days) exerted a phenothiazine-like effect in mice, reducing amphetamine-induced aggregation toxicity and enhancing pentobarbital-induced hypnosis.