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G A Mickley

Publications and source records attributed to G A Mickley.

At least 37 records · Page 2Linked to original sources
PubMed1986

Brain areas involved in production of morphine-induced locomotor hyperactivity of the C57B1/6J mouse.

Previous studies reveal a dose-dependent increase in locomotor activity of the C57B1/6J mouse after administration of morphine or amphetamine. Concurrent partial lesions of both the dorsomedial caudate and lateral septal nuclei resulted in a significant decrease in morphine-induced, but not amphetamine-induced, hyperactivity. Concurrent partial lesions of the nucleus accumbens and stria terminalis produced only a nonsignificant decrease in the morphine-induced hyperactivity. Lesions of the individual brain structures did not significantly affect the morphine-induced locomotor hyperactivity. Microinjections of the opiate antagonist naloxone into discrete portions of the caudate and septal nuclei produced suppression of the morphine-induced hyperactivity response without affecting the hyperactivity caused by amphetamine injections. Only a slight suppression of morphine-induced locomotion was produced when naloxone was injected into the nucleus accumbens and stria terminalis. These data suggest that portions of the caudate and septum may be involved in the mediation of morphine-induced hyperactivity in the C57B1/6J mouse.

Amphetamine↗
PubMed1986

Histamine H2 receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse.

Morphine-induced locomotor hyperactivity of the C57BL/6J mouse was challenged with intracranial injections of antihistamines or the opiate antagonist naloxone. When cimetidine (H2 receptor blocker) was injected into the nucleus accumbens/stria terminalis, it significantly reduced opiate-stimulated locomotion. However, ventricular injections of cimetidine did not significantly alter either morphine or amphetamine hyperactivity, nor did cimetidine depress spontaneous locomotion. Although naloxone eliminated morphine-induced locomotion when injected into either the nucleus accumbens or the ventricles, chlorpheniramine (H1 receptor blocker) failed to reduce this behavior. These data suggest that opiate-stimulated locomotion of the C57BL/6J mouse may be partially mediated by histamine H2 receptors of the nucleus accumbens or closely adjacent structures.

Amygdala↗
PubMed1986

Stimulation of brain muscarinic acetylcholine receptors acutely reverses radiogenic hypodipsia.

A sufficiently large dose of ionizing radiation produces changes in water consumption. However, the direction, durations, and physiological substrates of these alterations remain in question. Here we report a 5-d hypodipsia in rats exposed to 600 rads 60Co but a more transient, albeit larger, reduction in drinking after 1000 60Co. Brain cholinergic neurons have been implicated as mediators of thirst. Therefore, we explored the role of hypothalamic muscarinic receptors in the production of radiation-induced hypodipsia. This was accomplished through the intrahypothalamic injection of carbachol (a muscarinic agonist) or atropine (a muscarinic antagonist) in irradiated rats. Intracranial carbachol produced acute reversal of radiogenic hypodipsia while atropine potentiated the hypodipsia. These post-irradiation drug-induced behaviors were similar to those observed after the same drug treatments before irradiation. Since cholinergic neuronal functions persist and are labile (can be pharmacologically stimulated and blocked) after irradiation, this suggests that other neuronal systems and/or neurochemicals may be more prominently involved in radiogenic hypodipsia.

Animals↗
PubMed1985

Quaternary naltrexone reverses morphine-induced behaviors.

This study explored the relative role of the peripheral and central nervous systems (CNS) in the production of morphine-induced behavioral changes. Toward this end we used a quaternary derivative of an opiate antagonist (naltrexone methobromide, NM) that presumably does not cross the blood-brain barrier. Naltrexone methobromide (20, 40 and 80 mg/kg, IP) was used to challenge the stereotypic locomotion, analgesia and elevated "Straub" tail response observed in C57BL/6J mice after a 30-mg/kg (IP) injection of morphine. The quaternary derivative of naltrexone reversed the locomotor hyperactivity, "Straub" tail and analgesia normally observed in the opiate-treated C57BL/6J mouse. The data reported here, if taken at face value, suggest an important role for peripheral opiate receptors in morphine-induced behavioral changes. However, these conclusions are contingent on further research to more fully evaluate NM's capacity to cross the blood-brain barrier of the C57BL/6J mouse.

Animals↗
PubMed1983

Changes in morphine self-administration after exposure to ionizing radiation: evidence for the involvement of endorphins.

Recent findings have implicated endogenous opiates in radiation-induced behavioral change. The present experiment further investigated this hypothesis by observing alterations in morphine self-administration after irradiation. Under the presumption that the release of endogenous opiates would decrease the need for exogenously supplied morphine, we hypothesized that after radiation exposure morphine-experienced mice would self-administer less of the opiate. C57BL/6J mice had continuous access to two drinking flasks which contained either water or morphine in saccharine water. Irradiated mice drank significantly less morphine than did sham-irradiated controls. This decrease was naloxone-reversible and could not be entirely attributed to a generalized radiogenic hypodipsia or taste aversion. These results are consistent with the hypothesis that radiation-induced behavioral changes may be due, in part, to the fluctuations of endogenous opiates.

Animals↗
PubMed1983

Evidence for endorphin-mediated cross-tolerance between chronic stress and the behavioral effects of ionizing radiation.

C57BL/6J mice exhibit a naloxone-reversible locomotor hyperactivity after exposure to ionizing radiation. These data implicate endogenous opiates in this radiogenic behavioral change. Similarly, endorphins mediate analgesia produced by chronic stress (e.g., foot shock or restraint) and levels of plasma Beta-endorphin are elevated following exposure to acute stress. Therefore, the present study sought to determine if behavioral cross-tolerance could be obtained between endorphin-producing stressors and radiation exposure. Repeated pretreatment with foot shock or restraint subsequently inhibited the locomotor-activating effects of radiation. These data are consistent with the hypothesis that cross-tolerance developed between the effects of stress-induced endogenous opiate release and the radiation-induced release of endorphins.

Animals↗
PubMed1983

Endogenous opiates mediate radiogenic behavioral change.

Exposure of C57BL/6J mice to ionizing radiation caused stereotypical locomotor hyperactivity similar to that produced by morphine. Naloxone administration prevented this radiation-induced behavioral activation. These results support the hypothesis that endorphins are involved in some aspects of radiogenic behavioral change.

Animals↗
PubMed1983

Ionizing radiation alters beta-endorphin-like immunoreactivity in brain but not blood.

Previous behavioral and pharmacological studies have implicated endorphins in radiation-induced locomotor hyperactivity of the C57BL/6J mouse. However, the endogenous opiate(s) responsible for this behavioral change have not been identified. The present study measured beta-endorphin-like immunoreactivity (beta-END-LI) in brain, blood, and combined brain and pituitary samples from irradiated and sham-irradiated C57BL/6J mice. After radiation exposure, levels of beta-END-LI decreased significantly in the brain. A similar, but not statistically significant, decline was measured in combined brain and pituitary samples. Concentrations of blood beta-END-LI were not changed by irradiation. These radiogenic changes in beta-END-LI are in some ways similar to those observed after other stresses. However, radiation-induced locomotor hyperactivity may be mediated more by alterations of beta-END-LI in the brain than in the periphery. Other endogenous opiate systems may also contribute to this behavioral change in the C57BL/6J mouse.

Animals↗
PubMed1983

Morphine tolerance offers protection from radiogenic performance deficits.

When rats are exposed to a sufficiently large dose of ionizing radiation they exhibit lethargy, hypokinesia, and deficits in performance. These and other behavioral changes parallel those often observed in this species after a large dose of morphine. Since the release of endogenous opiates has been implicated in some stress reactions, we sought to determine if they might play a part in radiogenic behavioral deficits. Rats were trained to criterion on a signaled avoidance task. Some subjects were then implanted with a pellet containing 75 mg of morphine. Other animals received placebo implants. Over a number of days, morphine tolerance was evaluated by measurement of body temperature changes. Prior to 2500 rad 60Co exposure or sham irradiation, morphine (or placebo) pellets were removed. Twenty-four hours later rats were retested to assess their performance on the avoidance task. Morphine-tolerant subjects performed significantly better than the irradiated placebo-implanted group and no differently than morphine-tolerant/sham-irradiated animals. Morphine tolerance seems to provide a degree of behavioral radiation resistance. These data are consistent with the hypothesis that endogenous opiate hyperexcretion may play some part in the behavioral deficits often observed after irradiation.

Animals↗
PubMed1982

Radiogenic changes in the behavior and physiology of the spontaneously hypertensive rat: evidence for a dissociation between acute hypotension and incapacitation.

Immediately following exposure to a sufficiently large dose of ionizing radiation, rats and several other species experience a transient period of acute hypotension and an accompanying deficit in performance. Although significant correlations have been reported between the drop in blood pressure and the early transient incapacitation (ETI) and a causal relationship has been suggested, the extent to which hypotension precipitates the occurrence of the behavioral deficits remains uncertain. The present experiments investigated both radiogenic blood pressure and performance changes in a strain of rat bred for hypertension (spontaneously hypertensive rat: SHR) in order to determine if high blood pressure might attenuate ETI. Although male SHRs experienced a severe ETI and a drop in blood pressure, much of the data is inconsistent with the hypothesis that hypotension causes performance decrements. In an additional series of studies, blood volume and serum chemistry data were analyzed. Male SHRs were significantly higher than normotensive controls on several blood chemistry determinations. Exposure to ionizing radiation, more often than not, enhanced these differences. These results could not be explained on the basis of radiogenic blood volume fluctuations.

Animals↗
PubMed1981

Antihistamine provides sex-specific radiation protection.

Rats suffer an early transient performance decrement immediately after a sufficiently large dose of ionizing radiation. However, it has been shown that males experience a more severe incapacitation than females. This sex difference has been attributed to the low estrogen levels in the male. In support of this notion, supplemental estrogens in castrated male rats have produced less-severe performance decrements post-irradiation. Antihistamines have also previously been shown to alleviate radiation's effect on behavior. The present study revealed that antihistamines are only effective in altering the behavioral incapacitation of sexually intact male subjects. This contrasts with previous work which indicates that estrogens can only benefit gonadectomized rats. These findings suggest that different mechanisms may underly antihistamine and estrogen radiation protection.

Animals↗
PubMed1979

Yohimbine blocks lateral hypothalamus-mediated behaviors.

There exist behavioral and physiological similarities between rats injected with yohimbine and those with lesions of the lateral hypothalamus. The present study sought to determine if behaviors mediated by the lateral hypothalamus would be significantly altered by yohimbine. Deficits in performance of an active avoidance task have been observed after lateral hypothalamic lesions. Likewise, in the present experiment, yohimbine significantly reduced the ability of trained rats to perform in a similar paradigm. Systemic injections of yohimbine caused decrements in lateral hypothalamic self-stimulation behaviors as well as in locomotor activity produced by lateral hypothalamic stimulation. Similar behaviors mediated by the substantia nigra were relatively unaltered by yohimbine. A final experiment revealed that yohimbine reduces the enhanced glucose utilization normally observed at the lateral hypothalamus during electrical stimulation. These data support the view that the lateral hypothalamus may be an important target of yohimbine's CNS actions.

Animals↗
PubMed1979

Differential effects of localized lesions of n. accumbens on morphine- and amphetamine-induced locomotor hyperactivity in the C57BL/6J mouse.

Mice of the C57BL/6J strain became hyperactive to increasing doses of morphine sulfate. This response was similar to locomotor hyperactivity induced by amphetamine. Lesions and chemical blockade of posterior n. accumbens abolished amphetamine-induced hyperactivity and reduced but did not abolish the morphine response. These experiments demonstrate that the response to the two drugs is mediated by overlapping but noncongruent neural systems.

Amphetamine↗
PubMed1978

Movement induced in cataleptic rats: differential effects produced by electrical stimulation of the lateral hypothalamus, substantia nigra, and reticular formation.

Haloperidol catalepsy can be countered by electrical stimulation of the lateral hypothalamus (LH) and, to a lesser extent, the reticular formation (RH). Substantia nigra (SN) stimulation proved to be least effective in this regard. Dissociation between behavioral arousal and cortical EEG during stimulation of the RF in cataleptic rats was observed.

Animals↗
PubMed1978

Persistence of lateral hypothalamic-mediated behaviors after a supralethal dose of ionizing radiation.

After exposure to 10 krad of high-energy electrons, rats experience an early transient incapacitation characterized by symptoms similar to those associated with lateral hypothalamic lesions: akinesia and decrements in various motivated behaviors. Experimenter-imposed electrical stimulation of the lateral hypothalamus in akinetic, irradiated animals produced a locomotor response similar to that seen in unexposed rats. Furthermore, when allowed to self-stimulate, the irradiated subjects persisted in vigorous self-stimulation of the lateral hypothalamus while self-stimulation rates of other subcortical sites showed marked attenuation. The lateral hypothalamus is apparently less sensitive to ionizing radiation than are the other subcortical structures sampled.

Animals↗
PubMedDate not supplied

Progressive behavioral changes during the maturation of rats with early radiation-induced hypoplasia of fascia dentata granule cells.

Localized exposure of the neonatal rat brain to X-rays produces neuronal hypoplasia specific to the granule cell layer of the hippocampal dentate gyrus. This brain damage causes locomotor hyperactivity, slowed acquisition of passive avoidance tasks and long bouts of spontaneous turning (without reversals) in a bowl apparatus. Here we report how these behavioral deficits change as a function of subject aging and behavioral test replications. Portions of the neonatal rat cerebral hemispheres were X-irradiated in order to selectively damage the granule cells of the dentate gyrus. The brains of experimental animals received a fractionated dose of X rays (13 Gy total) over postnatal days 1 to 16 and control animals were sham-irradiated. Rats between the ages of 71-462 days were tested 3 separate times on each of the following 3 behavioral tests: 1) spontaneous locomotion, 2) passive avoidance acquisition, and 3) spontaneous circling in a large plastic hemisphere. Rats with radiation-induced damage to the fascia dentata exhibited long bouts of slow turns without reversals. Once they began, irradiated subjects perseverated in turning to an extent significantly greater than sham-irradiated control subjects. This irradiation effect was significant during all test series. Moreover, in time, spontaneous perseverative turning was significantly potentiated in rats with hippocampal damage but increased only slightly in controls. Early radiation exposure produced locomotor hyperactivity in young rats. While activity levels of controls remained fairly stable throughout the course of the experiment, the hyperactivity of the irradiated animals decreased significantly as they matured.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗