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J L Meyerhoff

Publications and source records attributed to J L Meyerhoff.

At least 73 records · Page 4Linked to original sources

Non-cholinergic neurotoxic effects of AF64A in the substantia nigra.

Ethylcholine aziridinium ion (AF64A), a putative specific cholinergic neurotoxin, was unilaterally injected into the substantia nigra of male rats. One week following injection, rats that were challenged with apomorphine exhibited ipsilateral circling behavior. After two weeks, rats were sacrificed and corpus striatum and combined n. accumbens plus o. tubercle were assayed for dopamine. Striatal dopamine levels were depleted by 50%. Histological examination showed that AF64A caused extensive damage at the injection site. These data indicate that injection of AF64A into the substantia nigra can result in damage to dopaminergic neurons.

Animals↗

Adrenalectomy abolishes the stress-induced increase in pituitary cyclic AMP.

We have previously demonstrated that various stressors increase pituitary cyclic AMP in vivo in the rat. In the course of studying the mechanisms mediating this response, we examined the effect of bilateral adrenalectomy on footshock-induced increases in pituitary cyclic AMP. In unoperated rats, intermittent footshock markedly increased pituitary levels of cyclic AMP and plasma levels of corticosterone and prolactin. Adrenalectomy completely abolished the stress-induced increase in pituitary cyclic AMP. The marked increase in plasma prolactin following footshock was not affected by adrenalectomy. Our results indicate that adrenal factors are involved in the stress-induced increase in pituitary cyclic AMP.

Adrenalectomy↗

Biochemical indices of reactivity and habituation in rats with hippocampal lesions.

The response of rats with hippocampal lesions to acute and repeated footshock stress was assessed by measurement of pituitary cyclic AMP, plasma corticosterone and plasma prolactin. Levels of pituitary cyclic AMP and plasma prolactin and corticosterone were similar in never-shocked sham controls, and never-shocked hippocampal and neocortical lesion groups. Acute first time shock markedly elevated all measured stress indices with no statistically significant differences observed among surgical groups. In rats subjected to repeated stress (one 15 min footshock session per day for 10 days) and sacrificed 24 hours after the last shock session, levels of pituitary cyclic AMP and plasma hormones were similar to levels in never-shocked shams with the exception of the hippocampal animals. The rats with hippocampal lesions had higher levels of pituitary cyclic AMP, plasma corticosterone and plasma prolactin compared to never-shocked animals. We suggest that these data reflect a hyperreactive response of the hippocampal animals to a situation previously associated with shock. Finally, rats in all surgical groups subjected to repeated stress and sacrificed immediately after the last shock session showed a diminished cyclic AMP response to the stressor as compared to first footshock session response, demonstrating a habituation to the stressor as measured by this index. No differences in habituation were observed among hippocampal, neocortical and sham groups. Plasma hormone responses did not habituate in any group. These data support the behavioral observations of hyperreactivity in hippocampal animals and indicate that hippocampal animals are able to habituate to repeated stressful stimuli.

Animals↗

Behavioral and neurochemical effects of intraventricular AF64A administration in rats.

Ethylcholine aziridinium ion solution (AF64A), a putative specific cholinergic neurotoxin, was injected bilaterally into the lateral ventricles of rats. Following administration of 3 or 6 nmoles of AF64A, drinking and eating were depressed but returned to normal levels after several days; increased activity in the 6 nmole group persisted throughout the 21 days of observations. Performance on complex place and cue tasks indicated that injected animals were impaired in reference memory only on the place task, but working memory was impaired on both tasks. Neurochemical measurements in a separate group of animals one week after AF64A injections found large depletions of acetylcholine in hippocampus and corpus striatum, but not depletions of norepinephrine (hippocampus) or dopamine (striatum). Histological examination of the injection site revealed extensive damage to the fimbria-fornix similar to that seen after electrolytic lesions. Since the behavorial and neurochemical changes are similar to those previously found following fimbria-fornix lesions, it is concluded that the present results are possibly due to non-specific lesion effects of the neurotoxin rather than a specific effect on cholinergic systems.

Acetylcholine↗

Regional brain and pituitary cyclic nucleotide response following central cholinergic stimulation in rats chronically exposed to lead.

Long Evans rats were exposed continuously to lead (1,000 ppm of lead acetate in the drinking water of dam or weanling) throughout gestation, lactation and until sacrifice at 60 days of age. A matched group of control animals was exposed to distilled water. On the day of sacrifice, control and lead treated animals were administered methylatropine 40 min. and oxotremorine (a muscarinic agonist) 10 min. prior to sacrifice by microwave irradiation. Locomotor activity was monitored during the 10 min. immediately preceding sacrifice. Levels of cyclic AMP and cyclic GMP were determined in 21 brain regions by radioimmunoassay. Locomotor activity following oxotremorine was significantly reduced in both lead treated and control animals. Levels of cyclic GMP were increased in septal region and frontal cortex and reduced in cerebellum and inferior colliculus of both groups of animals. The level of cyclic AMP in the pituitary increased 20-25 fold with a greater response noted in lead treated rats. Elevations of cyclic AMP were also noted in the interpeduncular nucleus, corpus striatum and substantia nigra in both groups. These data suggest that the cellular response to a muscarinic agonist was significantly affected by chronic exposure to lead in the pituitary but not in the remainder of the central nervous system.

Animals↗

Effects of chronic lead exposure on release of endogenous catecholamines: a preliminary communication.

The release of endogenous dopamine and norepinephrine from six brain regions (cortex, hippocampus, hypothalamus, striatum, s. nigra, n. accumbens-o. tubercle) of chronically lead-exposed rats was compared to release from controls. Prenatal and postnatal chronic lead intoxication was induced by 1000 ppm lead acetate in the drinking water of dams 70 days prior to mating and throughout gestation and lactation. Offspring were also maintained on 1000 ppm lead acetate until sacrificed at approximately 60 days of age. Release was measured in vitro from tissue minces prepared from both lead-exposed and control rats. There were no significant differences in spontaneous or potassium-stimulated norepinephrine release between lead-exposed and control rats. Potassium and amphetamine both stimulated striatal dopamine release; however, no marked differences between lead-exposed and control tissue were seen. Potassium-stimulated release of dopamine from the nucleus accumbens-olfactory tubercle area was increased in the lead-exposed animals. This is interesting in light of the postulated role of the n. accumbens in the central regulation of motor activity and the reported alterations in activity in lead-exposed rodents.

Animals↗

Graded footshock stress elevates pituitary cyclic AMP and plasma beta-endorphin, beta-LPH corticosterone and prolactin.

Male rats were subjected to 15 min of various intensities of footshock current (0.0, 0.2, 0.4, 0.8, 1.6, 2.4, 3.2m A) on a variable interval schedule with an average intershock interval of 30 sec (30 shocks/15 min session). Each shock lasted 5 sec. Animals were sacrificed immediately after being removed from the shock box. Two similar studies were conducted. In the first experiment, rats were sacrificed by microwave irradiation and pituitary cyclic AMP levels were determined. In the second study, rats were decapitated and plasma hormones (prolactin, corticosterone, beta-endorphin, beta-LPH) were measured by radioimmunoassay. Although all biochemical indices of stress measured increased as shock intensity increased, some differences among the substrates measured were observed with respect to threshold intensity, range of proportional response and maximal response.

Animals↗

Comparison of stress response in male and female rats: pituitary cyclic AMP and plasma prolactin, growth hormone and corticosterone.

Three potent stressors (forced running, immobilization, and footshock) were found to increase levels of cyclic AMP in the pituitaries of both female and male rats. The pituitary cyclic AMP response in females was generally similar to that observed in males. The tested stressors elevated both plasma corticosterone and prolactin and decreased plasma growth hormone. Plasma corticosterone rose more rapidly in females than in males following stress. Control growth hormone levels were higher in male rats. There was no clear cause and effect relationship between elevations of pituitary cyclic AMP and changes in plasma levels of prolactin, corticosterone, and growth hormone.

Animals↗

Effects of repeated stress on pituitary cyclic AMP, and plasma prolactin, corticosterone and growth hormone in male rats.

The effects of five putative stressors (saline injection, cold exposure, forced running, immobilization, and footshock) on levels of pituitary cyclic AMP, plasma prolactin, corticosterone and growth hormone were examined. In naive rats exposed to 15 min of these stressors for the first time, running, immobilization and footshock increased levels of pituitary cyclic AMP, plasma corticosterone and prolactin and decreased growth hormone, typical of stress response in the rat. Cold exposure only increased corticosterone and saline injection did not affect any measured parameter. In rats chronically exposed to the same stressor (once a day for 15 min) for 10 days immediately prior to the experiment, an attenuated pituitary cyclic AMP and plasma prolactin response was seen upon application of 15 min of that stressor on the day of the experiment, compared to the responses observed in the naive rats.

Animals↗

Cyclic AMP and cyclic GMP response to stress in brain and pituitary: stress elevates pituitary cyclic AMP.

Male rats were exposed to six stressors (saline injection, cold, forced running, Formalin injection, immobilization, electric footshock) for 15, 30, or 60 min. Following sacrifice by microwave irradiation, cyclic AMP and cyclic GMP levels were measured in pituitary, pineal and 8 regions of rat brain. All stressors except saline increased plasma corticosterone, plasma prolactin and pituitary cyclic AMP levels compared to control animals. The magnitude of the pituitary cyclic AMP response was highly correlated with the intensity of the stress as determined by the levels of plasma prolactin. Electric footshock increased pituitary cyclic AMP levels over 10 fold and plasma prolactin over 60 fold. Cyclic AMP levels in other brain regions were not altered. Cerebellar cyclic GMP was increased only by stressors that involved increased motor activity.

Animals↗