Abstract
Although immature rats and mice generally demonstrate poor behavioral inhibitory capacities, some recent evidence may indicate the presence of substantial inhibitory control. The present experiment investigated the possibility that gamma-aminobutyric acid (GABA) systems may mediate some behavioral inhibition during early development. Mice 9 – 100 days old were injected with the GABA-elevating agent amino-oxyacetic acid (AOAA) and tested for behavioral activity. High levels of locomotor activity characteristic of immature control mice were attenuated following AOAA injection, whereas AOAA had little effect on the activity of adult mice. Moreover, AOAA produced a period of rebound hyperactivity for young but not for adult mice. These findings suggest that although GABA systems may mediate early behavioral inhibition, coordination between excitatory and inhibitory capacities matures slowly. In a second experiment the dopamine-β-hydroxylase inhibitor FLA-63 prevented rebound hyperactivity in young mice pretreated with AOAA, suggesting that the excitatory component may be mediated by noradrenergic systems.
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References
Al-Ani, A. T., Tunnicliff, G., Rick, J. T., Kerkut, G. A.: GABA production, acetylcholinesterase activity and biogenic amine levels in brain for mouse strains differing in spontaneous activity and reactivity. Life Sci. 9, 21–27 (1970)
Benton, D., Rick, J. T.: The effect of increased brain GABA produced by amino-oxyacetic acid on arousal in rats. Psychophamacology 49, 85–89 (1976)
Campbell, B. A., Lytle, L. D., Fibiger, H. C.: Ontogeny of adrenergic arousal and cholinergic inhibitory mechanisms in the rat. Science 166, 637–638 (1969)
Campbell, B. A., Mabry, P. D.: The role of catecholamines in behavioral arousal during ontogenesis. Psychopharmacologia 31, 253–264 (1973)
Campbell, B. A., Raskin, L. A.: Ontogeny of behavioral arousal: The role of environmental stimuli. J. Comp. Physiol. Psychol. 92, 176–184 (1978)
Cott, J., Carlsson, A., Engel, J., Lindqvist, M.: Suppression of ethanol-induced locomotor stimulation by GABA-like drugs. Naunyn Schmiedebergs Arch. Pharmacol. 295, 203–209 (1976)
Coyle, J. T., Jr.: Development of the central catecholaminergic neurons. In: The neurosciences: Third study program. F. O. Schmitt, F. G. Worden, eds., pp. 877–884. Cambridge: MIT 1974
Coyle, J. T., Enna, S. J.: Neurochemical aspects of the ontogenesis of GABA nergic neurons in the rat brain. Brain Res. 111, 119–133 (1976)
Davies, L. P., Johnston, G. A. R., Stephanson, A. L.: Postnatal changes in the potassium-stimulated, calcium-dependent release of radioactive GABA and glycine from slices of rat central nervous tissue. J. Neurochem. 25, 387–392 (1975)
Flexner, J. B., Flexner, L. B.: Effect of two inhibitors of dopamine β-hydroxylase on maturation of memory in mice. Pharmacol. Biochem. Behav. 5, 117–121 (1976)
Freed, W. J., Michaelis, E. K.: Effects of intracisternal GABA or glutamic acid upon behavioral activity in the rat. Pharmacol. Biochem. Behav. 5, 11–14 (1976)
Gaitonde, M. K., Festing, M. F. W.: Brain glutamic acid decarboxylase and open field activity in ten inbred strains of mice. Brain Res. 103, 617–621 (1976)
Himwich, W. A.: Developmental neurobiology. Springfield: Thomas 1970
Kety, S. S.: The biogenic amines in the central nervous system: Their possible roles in arousal, emotion, and learning. In: The neurosciences: Second study program, F. O. Schmitt, ed., pp. 324–336. New York: Rockefeller University 1970
Kuriyama, K., Roberts, E., Rubinstein, M. K.: Elevation of γ-aminobutyric acid in brain with amino-oxyacetic acid and susceptibility to convulsive seizures in mice: A quantitative re-evaluation. Biochem. Pharmacol. 15, 221–236 (1966)
Mabry, P. D., Campbell, B. A.: Ontogeny of serotonergic inhibition of behavioral arousal in the rat. J. Comp. Physiol. Psychol. 86, 193–201 (1974)
Murphy, J. M., Nagy, Z. M.: Development of cholinergic inhibitory capacities in the hyperthyroid mouse. Pharmacol. Biochem. Behav. 5, 449–456 (1976)
Nagy, Z. M., Murphy, J. M., Ray, D.: Development of behavioral arousal and inhibition in the Swiss-Webster mouse. Bull. Psychon. Soc. 6, 146–148 (1975)
Randall, P. K., Campbell, B. A.: Ontogeny of behavioral arousal in rats: Effect of maternal and sibling presence. J. Comp. Physiol. Psychol. 90, 453–459 (1976)
Ray, D., Nagy, Z. M.: Emerging cholinergic mechanisms and ontogeny of response inhibition in the mouse. J. Comp. Physiol. Psychol. 92, 335–349 (1978)
Rick, J. T., Tunnicliff, G., Kerkut, G. A., Fulker, D. W., Wilcock, J., Broadhurst, P. L.: GABA production in brain cortex related to activity and avoidance behaviour in eight strains of rat. Brain Res. 32, 234–238 (1971)
Roberts, E.: Coordination between excitation and inhibition: Development of the GABA system. In: Sleep and the maturing nervous system, C. D. Clemente, D. P. Purpura, F. E. Mayer, eds., pp. 79–98. New York: Academic Press 1972
Roberts, E.: Disinhibition as an organizing principle in the nervous system: The role of the GABA system. Application to neurologic and psychiatric disorders. In: GABA in nervous system function, E. Roberts, T. N. Chase, D. B. Tower, eds., pp. 515–539. New York: Raven 1976
Schildkraut, J. J., Kety, S. S.: Biogenic amines and emotion. Science 156, 21–30 (1967)
Sze, P. Y.: Possible repression of L-glutamic acid decarboxylase by gamma-aminobutyric acid in developing mouse brain. Brain Res. 19, 322–325 (1970)
Tapia, R., Sandoval, M.-E., Contreras, P.: Evidence for a role of glutamate decarboxylase activity as a regulatory mechanism of cerebral excitability. J. Neurochem. 24, 1283–1285 (1975)
Tunnicliff, G., Wimer, C. C., Wimer, R. E.: Relationships between neurotransmitter metabolism and behaviour in seven inbred strains of mice. Brain Res. 61, 428–434 (1973)
Tunnicliff, G., Wimer, C. C., Wimer, R. E.: Brain γ-aminobutyric acid metabolism and behaviour in the mouse and rat. Gen. Pharmacol. 7, 67–69 (1976)
Wallach, D. P.: Studies on the GABA pathway: The inhibition of γ-aminobutyric acid-α-ketoglutaric acid transaminase in vitro and in vivo by U-7524 (amino-oxyacetic acid). Biochem. Pharmacol. 5, 323–331 (1961)
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Murphy, J.M., Meeker, R.B., Porada, K.J. et al. GABA-mediated behavioral inhibition during ontogeny in the mouse. Psychopharmacology 64, 237–242 (1979). https://doi.org/10.1007/BF00496069
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DOI: https://doi.org/10.1007/BF00496069