Analeptic effect of TRH in rats selectively bred for differential CNS sensitivity to ethanol.
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Alcoholic Intoxication↗
Biomedical subjects
M A Segall
Publications and source records attributed to M A Segall.
Behavioral effects of mouse interferons-alpha and -gamma and human interferon-alpha in mice.
Behavioral effects of murine interferon-alpha and -gamma were explored using a well-characterized system for detecting interferon effects. In addition, the effectiveness of human interferon-alpha was determined. Mouse gamma-interferon decreased activity and food-related behavior, effects that were similar to the effects of mouse alpha-interferon. Equivalent doses of the human preparation had little effect upon these measures in mice. Some common action of alpha- and gamma-interferon is likely responsible for the similar effects seen for the two molecules. Low effectiveness of the human preparation in mice was predicted due to the differences in receptors between species.
Animals↗
Prostaglandins do not mediate interferon-alpha effects on mouse behavior.
Interferons play an important role in cell function as well as host defense against virus infection. Interferon-alpha stimulates cyclooxygenase-catalyzed prostaglandin synthesis. Therefore, a cyclooxygenase inhibitor was used to determine whether the behavioral effects of mouse interferon-alpha in mice are mediated by increased prostaglandin synthesis. Male DBA/2J mice were exposed to 1600 U/g mouse interferon-alpha, the buffer in which the interferon was diluted, 5 mg/kg of a cyclooxygenase inhibitor, indomethacin, or 5 mg/kg indomethacin plus 1600 U/g mouse interferon-alpha. As in previous studies, interferon decreased activity and food pellets obtained in the first 4 hours after administration. Indomethacin had no effect on this effect of interferon; therefore, we conclude that the behavioral effects of interferon are not mediated by the fever or anorectic effects of prostaglandins.
Animals↗
A test of conditioned taste aversion with mouse interferon-alpha.
Interferon-alpha treatment induces anorexia in cancer patients and in mice. The ability of interferon-alpha to induce a conditioned taste aversion (CTA) in mice was explored. Mice were injected with doses of interferon-alpha that had been shown to induce anorexia (M. A. Segall & L. S. Crnic, Behav. Neurosci., 1990; 1600 or 800 U/g of mouse) after being given a novel solution (chocolate milk). Neither dose of interferon resulted in a decrease of milk intake on the test day. To determine whether the known cognitive effects of interferon interfere with the ability of a mouse to learn CTA, a combined injection of interferon-alpha and LiCl (an illness-inducing agent) was given. The combination of interferon-alpha with LiCl did not interfere with the LiCl-induced CTA. Thus, any possible cognitive effects of interferon did not interfere with conditioned taste aversion. To test the possibility that repeated trials might establish a conditioned taste aversion to interferon, mice were given three conditioning trials spaced 3 days apart. No aversion developed. Doses of interferon-alpha that produce anorexia do not produce a conditioned taste aversion, indicating that separate mechanisms are activated in these two behaviors.
Animals↗
An animal model for the behavioral effects of interferon.
Interferon, which is produced during viral infections, has cognitive and neurological effects in humans. A dose of 1600 U/g of mouse interferon-alpha significantly depressed horizontal activity, head pokes into a food chamber, and food intake in mice 10 hr and 24 hr after injection. An 800 U/g dose had only slight effects on horizontal activity and food intake, whereas a 400 U/g dose had no effect. There was no evidence of sensitization to interferon when a second 400 U/g dose was given after the 1600 U/g dose. The results imply that mouse interferon-alpha can be used in mice as a model for studying the fatigue and anorexia produced by interferon.
Animals↗
Central mediation of naloxone-induced anorexia in the ventral tegmental area.
Central naloxone injections were used to show that endogenous opioids in the ventral tegmental area (VTA) regulate consumption of palatable foods. Peripheral injections of naloxone were more effective in reducing the consumption of a sweet solution in normally fed rats than in animals maintained at 85% of their free-feeding body weight. A dose of 10 micrograms/side naloxone injected into the VTA reduced consumption in normally fed rats, whereas a dose of 25 micrograms/side did the same in food-restricted animals. The inactive isomer, (+) naloxone, did not reduce consumption; the effect has chemical specificity. Naloxone injected 0.5, 1.0, or 2.0 mm above the VTA did not reduce consumption; the effect has anatomical specificity. Naloxone effectively decreases the eating of palatable foods, but not eating for survival. This has important implications for the use of opioid antagonists in weight-loss programs.
Animals↗
Development of neurochemical and behavioral sensitivity to ethanol in long-sleep and short-sleep mice.
The postnatal development of certain neurochemical correlates of CNS ethanol sensitivity was examined in the long-sleep (LS) and short-sleep (SS) mice. The differences in sensitivity to the motor-incoordinating and hypothermic effects of ethanol emerged during the second and third weeks of life. Prior studies have shown the sleep time differences between LS and SS mice became significant at 8-10 days of age whereas the present results established that the differences in ethanol-induced hypothermia became prominent at 12-16 days of age. Previous results from our laboratory suggested that the greater CNS ethanol behavioral sensitivity (sleep time and hypothermia) of LS mice is related to the greater ethanol-induced depression of brain monoamine synthesis in the LS line. The timing of the developmental changes in neurochemical ethanol sensitivity in LS and SS mice was found to parallel that found in the development of behavioral ethanol sensitivity as follows. Ethanol-induced decreases in in vivo tyrosine hydroxylase activity in the cerebellum, hypothalamus, and brain stem did not differ between LS and SS mice at postnatal day 8, but became substantially greater in LS mice between postnatal days 8 and 12, coincident with the appearance of the greater sleep times of LS mice. Likewise, ethanol-induced decreases in in vivo tryptophan hydroxylase activity in the dorsal raphe and hypothalamus, which were similar in LS and SS mice at postnatal days 8 and 12, became significantly greater in LS mice by postnatal day 16, the age at which their increased sensitivity to ethanol-induced hypothermia appeared.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of neonatal thyroid hormone alterations in CNS ethanol sensitivity in adult LS and SS mice.
LS and SS mice develop their differential sensitivity to the motor-incoordinating and hypothermic effects of ethanol at 10-16 days after birth, when thyroid hormones (T4) show a transient peak. This rise in the thyroid hormones is an important element in the normal development of monoaminergic systems and thyroid hormones reach a significantly higher level in the less ethanol-sensitive SS mice than in the more ethanol-sensitive LS mice. Previous investigation have suggested the differential ethanol response of brain monoaminergic neuronal systems in adult LS and SS mice may be related to this development difference in thyroid status. To test the hypothesis that neonatal thyroid status can influence adult CNS ethanol sensitivity. LS and SS mice were treated neonatally with the thyrotropin-releasing hormone (TRH) and propylthiouracil (PTU) to enhance or diminish, respectively, thyroid status at this critical developmental period. The subsequent effect on adult CNS ethanol sensitivity was then determined. Contrary to expectations, both PTU and TRH administration attenuated the transient rise in plasma T4 levels at postnatal days 10-16 in LS mice and in both instances this was associated with decreased CNS ethanol sensitivity (sleep time and hypothermia) in adults. In SS mice, PTU treatment attenuated the postnatal rise in T4 levels as expected, whereas TRH treatment had no significant effect. However, neither neonatal treatment altered CNS ethanol sensitivity in adult SS mice. The decrease in ethanol-induced sleep times and hypothermia of neonatally treated LS mice was associated with an attenuation of ethanol-induced decreases in in vivo tyrosine and tryptophan hydroxylase activity that was not seen in the SS mice. These findings are consistent with the notion that the response of monoaminergic neuronal systems to ethanol is an important determinant of behavioral intoxication. However, the observation that neonatal administration of both TRH and PTU blunted the postnatal rise in thyroid levels in LS mice, yet both treatments resulted in a decrease in adult ethanol sensitivity in LS mice, indicates that the relationship between postnatal thyroid development and CNS ethanol sensitivity is more complex than originally hypothesized.
Adrenal Glands↗