Biomedical subjects
Publications and source records attributed to J L Meyerhoff.
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Rats subjected to electrolytic lesions of the ventral medial tegmentum (VMT) showed long-lasting increased locomotor activity in the open field compared to sham-operated controls. In addition to severe depletion of mesolimbic dopamine, the lesions also caused significant depletions of striatal dopamine, mesolimbic and striatal norepinephrine and striatal and hippocampal serotonin. Administration of d-amphetamine sulfate produced similar dose-response functions for locomotor activity in both VMT-lesioned and sham-operated rats despite the extensive depletion of dopamine in the VMT-lesioned rats. These results suggest that the mesolimbic dopamine pathway is not the sole substrate for amphetamine-stimulated locomotor activity. Electrolytic lesions of the VMT interrupt several neurotransmitter pathways which may produce complex and antagonistic effects on behavior.
The neuroendocrine and neurochemical responses of rats to 5 min of cold exposure versus 5 min of forced immobilization were determined and compared. We found that plasma hormones and brain neurochemical systems responded differently to the two different stressors. Plasma prolactin levels were elevated over 10-fold in the immolilized group, while rising only 2-fold in the cold stress group. Levels of corticosterone were significantly increased and growth hormone levels were decreased in both stressed groups as compared to controls. Levels of cyclic GMP were markedly elevated in 11 brain regions following cold exposure. Surprisingly, no elevation of cyclic GMP was found after forced immobilization. Cyclic AMP, norepinephrine, and dopamine levels throughout the 17 regions of brain examined showed no significant response to 5 min of either stressor. Lesions of the ventral medial tegmental area did not affect the cyclic GMP or neuroendocrine responses to cold stress. Lesion of the nucleus locus ceruleus did not affect the cyclic GMP response but significantly reduced growth hormone levels in the cold-stressed rats.
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.
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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.
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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.
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.
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