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Biomedical subjects

J L Meyerhoff

Publications and source records attributed to J L Meyerhoff.

At least 19 recordsLinked to original sources

Changes in brain levels of cyclic nucleotides and gamma-aminobutyric acid in barbiturate dependence and withdrawal.

Rats exposed to chronic intake of sodium barbital maintained high circulating levels of barbital in blood and brain and exhibited increased sensitivity ot audiogenic convulsions during the withdrawal period. Levels of gamma-aminobutyric acid (GABA), glutamate, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) were measured in selected brain regions after sacrifice with high power microwave inactivation. Cyclic GMP during chronic barbital administration was significantly lower than controls in most brain regions, especially the hindbrain. During the withdrawal period cyclic GMP in the cerebellum was significantly increased, while returning at least to control levels in all other regions. GABA throughout the brain tended to be reduced during barbital dependence, while cyclic AMP and glutamate levels remained unchanged in all groups. These results indicate a possible role for cyclic GMP in the mediation of the central nervous system response during barbiturate dependence and withdrawal.

Acoustic Stimulation

Dopamine diffusion after microwave fixation at 986 MHz.

It has been previously demonstrated by us that microwave irradiation at 2450 MHz causes diffusion of dopamine from rat brain regions of high dopamine concentration to contiguous regions low in dopamine. Because we have found that the heating pattern at 986 MHz is opposite to that seen at 2450 MHz, we attempted in the present study to eliminate DA diffusion by heating at 986 MHz. However, dopamine levels were elevated in frontal and parietal cortex, remainder of cortex, and amygdala after sacrifice by microwave irradiation at 986 MHz. Norepinephrine levels were unaffected by sacrifice method. Microwave-induced diffusion of certain substances must be considered in the interpretation of regional neurochemical data.

Animals

Cortisol secretion and clearance in the rhesus monkey.

Cortisol secretory patterns were studied in two chair-adapted rhesus monkeys by simultaneous measurement of plasma concentration and specific activity of cortisol after an iv bolus of 14C-labeled hormone. The results indicated that fluctuating plasma cortisol concentrations are the result of episodic secretion by the adrenal cortex. Specific activity changes during these spontaneous secretory bursts indicated occasional submaximal activity. In addition, cortisol secretory rates calculated during basal (20.4 mug/min) and ACTH-stimulated (28.4mug/min) conditions in a total of seven monkeys were significantly different (P less than 0.05), further demonstrating that spontaneous secretory bursts were usually sub-maximal. From plasma samples collected at 10 min intervals, a cortisol distribution t1/2 of 6 min and a clearance t1/2 of 66 min were found. The apparent volume of distribution for this hormone was 4.8 liters, a value far in excess of extracellular fluid volume estimates. The circadian pattern of plasma cortisol in these monkeys resembled that reported for man, but monkeys had twice as many episodic bursts and over twice the mean cortisol levels as man. However, the 24 h production rate was 10.5 mg, a value within the range of human production.

Adrenal Cortex

Regional levels of cyclic AMP in rat brain: pitfalls of microwave inactivation.

Techniques of in-vivo microwave irradiation to inactivate brain enzymes in rats were varied as to exposure configuration and output power. The rate at which metabolism was stopped was studied in various regions of the rat brain, using changes in levels of cyclic AMP and phosphodiesterase activity. Exposure times required to obtain stabilized levels of cyclic AMP varied in different brain regions, i.e., hypothalamus, cortex and cerebellum. Levels of cyclic AMP in selective regions of the brain decreased as more rapid inactivation was achieved. The authors identify important sources of variability of present microwave inactivation systems and the need for improved control of signficant microwave parameters.

3',5'-Cyclic-AMP Phosphodiesterases

Dopamine and norepinephrine levels in the nucleus accumbens, olfactory tubercle and corpus striatum following lesions in the ventral tegmentalarea.

Dopamine and norepinephrine levels were examined in 3 forebrain regions following unilateral lesions either in the ventral medial tegmental area (VMT) or in the substantia nigra. The dopamine and norepinephrine content of the nucleus accumbens, olfactory tubercle and corpus striatum were assayed ipsilaterally and contralaterally in unilaterally lesioned rats sacrificed 2, 5, 10, and 20 days after the placement of the lesions. In the nucleus accumbens and olfactory tubercle ipsilateral dopamine levels were significantly reduced below the contralateral levels at 2 days, and were decreased by 56% and 65%, respectively, 10 days after the lesion. A 30% reduction of dopamine levels occurred in corpus striatum as well, following lesions in the VMT. Lesions in the substantia nigra decreased ipsilateral dopamine levels by 68% in the corpus striatum, without affecting dopamine levels in the olfactory tubercle or nucleus accumbens. Norepinephrine levels on the side ipsilateral to the lesion did not significantly differ from contralateral levels in any of the 3 regions following lesions either in the VMT or in the substantia nigra. These results demonstrate the specificity of projection in the mesolimbic dopamine system as suggested by the original histofluorescence studies.

Animals

Effects of heroin on lever pressing for intracranial self-stimulation, food and water in the rat.

Male rats maintained with continuous access to levers for intracranial self-stimulation (ICSS), water, and food were subjected to five consecutive daily injections of heroin (5 mg/kg). Rates of lever pressing for ICSS were increased in 8 rats, 2--6 hrs after administration of heroin. Rates of lever pressing for water and food were not significantly changes during this period. Naloxone (5 mg/kg) pretreatment attenuated by 82% the facilitative effect of heroin on ICSS. A second group of 8 rats maintained at reduced ICSS rates failed to show an increase in lever pressing for ICSS with heroin. The facilitative effect of heroin described in this study is consistent with previously reported studies describing the effects of morphine on ICSS.

Animals