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Developmental changes in pharmacological responsivity of the acoustic startle reflex: Effects of picrotoxin

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Abstract

Using the acoustic startle reflex as the behavioral measure, qualitatively different responses to the GABA antagonist picrotoxin were obtained in developing rats before and after 21 days postnatal (PN) age. Dose-dependent increases in acoustic startle were seen following picrotoxin in PN day 15–16 rat pups. In contrast, dose-dependent decreases in startle following picrotoxin were observed in adult rats. The switch from excitation to inhibition of startle was found to occur abruptly on PN day 21. Excitatory responses to picrotoxin were also found in adult rats following localized infusions of picrotoxin into lumbar spinal cord regions, but not into the forebrain. These results give evidence that picrotoxin-sensitive sites that modulate increases in startle reflex behavior mature first and are analogous to sites in the adult spinal cord, whereas picrotoxin-sensitive sites that modulate decreases in startle reflex behavior mature later (≥PN day 21) and are localized in more rostral brain areas.

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References

  • Aghajanian GK, Bloom FE (1967) The formation of synaptic junctions in developing rat brains: A qualitative electron microscopic study. Brain Res 6:710–727

    Google Scholar 

  • Andrews PR, Johnston GAR (1979) GABA agonist and antagonists. Biochem Pharmacol 28:2697–2702

    Google Scholar 

  • Astrachan DI, Davis M (1981) Spinal modulation of the acoustic startle response: The role of norepinephrine, serotonin and dopamine. Brain Res 206:223–228

    Google Scholar 

  • Berry M (1974) Development of the cerebral neocortex of the rat. In: Gottlieb G (ed) Studies on the development of behavior and the nervous system. Academic, New York, pp 8–68

    Google Scholar 

  • Bowery NG, Hill DR, Hudson AL, Doble A, Middlemiss DN, Shaw J, Turnbull M (1980) (-)Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor. Nature 283:92–94

    Google Scholar 

  • Browner M, Ferkany JW, Enna SJ (1981) Biochemical identification of pharmacologically and functionally distinct GABA receptors in rat brain. J Neurosci 1:514–518

    Google Scholar 

  • Campbell B, Raskin L (1978) Ontogeny of behavioral arousal: The role of environmental stimuli. J Comp Physiol Psychol 92:176–184

    Google Scholar 

  • Chronwall B, Wolff JR (1980) Prenatal and postnatal development of GABA-accumulating cells in the occipital neocortex of rat. J Comp Neurol 190:187–208

    Google Scholar 

  • Coyle JT, Enna SJ (1976) Neurochemical aspects of the ontogenesis of GABAergic neurons in the rat brain. Brain Res 111:119–133

    Google Scholar 

  • Crain SM, Bornstein MB (1974) Early onset in inhibitory functions during synaptogenesis in fetal mouse brain cultures. Brain Res 68:351–357

    Google Scholar 

  • Davis M (1980) Neurochemical modulation of sensory-motor reactivity: acoustic and tactile startle reflexes. Neurosci Biobehav Rev 4:241–263

    Google Scholar 

  • Davis M, Astrachan DI, Kass E, (1980) Serotonin: Excitatory and inhibitory effects on behavioral reactivity measured with acoustic startle. Science 209:521–523

    Google Scholar 

  • Davis M, Gendelman DI, Tischler M, Gendelman PM (1982) A primary acoustic startle circuit: Lesion and stimulation studies. J Neurosci 2:791–805

    Google Scholar 

  • Evans RH (1978) The effects of amino acids and antagonists in the isolated hemisected spinal cord of the immature rat. Br J Pharmacol 62:171–176

    Google Scholar 

  • Gallager DW, Kehne JH, Davis M (1981) Developmental changes in pharmacological responsivity of the acoustic startle reflex. Soc Neurosci Abstr 7:403

    Google Scholar 

  • Iversen LL, Bloom FE (1972) Studies on the uptake of 3H-GABA and 3H-glycine in slices and homogenates of rat brain and spinal cord by electron microscopic autoradiography. Brain Res 41:131–143

    Google Scholar 

  • Jacobson M (1978) Developmental Neurobiology. Plenum, New York

    Google Scholar 

  • Johnston GAR (1978) Neuropharmacology of amino acid inhibitory transmitters. Annu Rev Pharmacol Toxicol (Copenh) 18:269–289

    Google Scholar 

  • Johnston GAR, Davies LP (1974) Postnatal changes in the high affinity uptake of glycine and GABA in the rat central nervous system. J Neurochem 22:101–105

    Google Scholar 

  • Kehne JH, Gallager DW, Davis M (1981) Strychnine: Brain stem and spinal mediation of excitatory effects on acoustic startle Eur J Pharmacol 76:177–186

    Google Scholar 

  • Lanier LP, Dunn AJ, van Hartesveldt C (1976) Development of neurotransmitters and their function in brain. In: Ehrenpreis S, Kopin IJ (eds) Reviews of neuroscience Raven, New York, pp 195–256

    Google Scholar 

  • Levi G, Coletti A, Raiteri M (1979) Modulation of GABA transport in nerve endings: Developmental aspects. In: Meisami E, Brazier MAB (eds) Neural growth and differentiation. Raven, New York, pp 91–111

    Google Scholar 

  • Mabry P, Campbell B (1977) Developmental psychopharmacology. In: Iversen LL, Iversen SD, Synder SH (eds) Handbook of Psychopharmacology. Plenum, New York, pp 393–444

    Google Scholar 

  • McLaughlin B, Wood J, Saito K, Barber R, Vaugh J, Roberts E, Wu JY (1974) The fine structural localization of glutamate decarboxylase in synaptic terminals of rodent cerebellum. Brain Res 76:311–391

    Google Scholar 

  • Murphy JM, Meeker RB, Porada KJ, Nagy ZM (1979) GABA-mediated behavioral inhibition during ontogeny in the mouse. Psychopharmacology 64:237–242

    Google Scholar 

  • Nistri A, Constanti A (1979) Pharmacological characterization of different types of GABA and glutamate receptors in vertebrates and invertebrates. Prog Neurobiol 13:117–235

    Google Scholar 

  • Nutt DJ, Cowen PJ, Batts CC, Grahame-Smith DG Green AR (1982) Repeated administration of subconvulsant doses of GABA antagonist drugs. I. Effect on seizure threshold (kindling). Psychopharmacology 76:84–87

    Google Scholar 

  • O'Brien J (1970) Lipids and myelination. In: Himwich WA (ed) Developmental neurobiology. Charles Thomas, Springfield, pp 262–282

    Google Scholar 

  • Olsen RW (1981) GABA-benzodiazepine-barbiturate receptor interactions. J Neurochem 37:1–13

    Google Scholar 

  • Palacios J, Nichoff D, Kuhar M (1979) Ontogeny of GABA and benzodiazepine receptors: Effects of Triton X-100, bromide and muscimol. Brain Res 179:390–395

    Google Scholar 

  • Parisi T, Ison J (1979) Development of the acoustic startle response in the rat: Ontogenetic changes in the magnitude of inhibition by prepulse stimulation. Dev Psychobiol 12:219–230

    Google Scholar 

  • Parisi T, Ison J, Kellog C (1978) Neonatal 6-hydroxydopamine: Effects on the development of the acoustic startle response and maturation of sensory systems. Soc Neurosci Abstr 4:122

    Google Scholar 

  • Perez-delaMora M, Possani LD, Tapia R, Teran L, Palacios R, Fuxe K, Hokfelt T, Ljungdahl A (1981) Demonstration of central γ-aminobutyrate-containing nerve terminals by means of antibodies against glutamate decarboxylase. Neuroscience 6:875–895

    Google Scholar 

  • Pickles HG (1979) Presynaptic γ-aminobutyric acid responses in the olfactory cortex. Br J Pharmacol 65:223–228

    Google Scholar 

  • Simmonds M (1978) Presynaptic actions of γ-aminobutyric acid and some antagonists in a slice preparation of cuneate nucleus. Br J Pharmacol 63:495–502

    Google Scholar 

  • Shnerson A, Willott JF (1980) Ontogeny of the acoustic startle response in C57BC/6J mouse pups. J Comp Physiol Psychol 94:136–140

    Google Scholar 

  • Thornburg J, Moore K (1976) Pharmacologically induced modifications of behavior and neurochemical development. In: Mirkin BL (ed) Perinatal pharmacology and therapeutics. Academic, New York, pp 269–354

    Google Scholar 

  • Unnerstall JR, Kuhar MJ, Niehoff DL, Palacios JM (1981) Benzodiazepine receptors are coupled to a subpopulation of γ-aminobutyric acid (GABA) receptors: Evidence for a qualitative autoradiographic study. J Pharmacol Exp Ther 218:797–804

    Google Scholar 

  • Vernadakis A, Woodbury D (1965) Cellular and extracellular spaces in developing rat brain: Radioactive uptake studies with chloride and inulin. Arch Neurol 12:284–293

    Google Scholar 

  • Vernadakis, A, Woodbury D (1969) The developing animal as a model. Epilepsia 10:163–178

    Google Scholar 

  • Weiss GT, Davis M (1976) Automated system for acquisition and reduction of startle response data. Pharmacol Biochem Behav 4:713–718

    Google Scholar 

  • Wong PTH, MacGeer EG (1981) Postnatal changes of GABAergic and glutamatergic parameters. Dev Brain Res 1:519–529

    Google Scholar 

  • Woodward DH, Hoffer BJ, Siggins GR, Bloom FE (1971) The ontogenetic development of synaptic junctions, synaptic activation and responsiveness to neurotransmitter substances in rat cerebellar Purkinje cells. Brain Res 34:73–97

    Google Scholar 

  • Yaksh TL, Rudy TA (1976) Chronic catheterization of the spinal subarachnoid space. Physiol Behav 17:1031–1036

    Google Scholar 

  • Zarbin MA, Wamsley JK, Kuhar MJ (1981) Glycine receptor: Light-microscopic autoradiographic localization of 3H-strychnine J Neurosci 1:532–547

    Google Scholar 

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Gallager, D.W., Kehne, J.H., Wakeman, E.A. et al. Developmental changes in pharmacological responsivity of the acoustic startle reflex: Effects of picrotoxin. Psychopharmacology 79, 87–93 (1983). https://doi.org/10.1007/BF00427790

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  • DOI: https://doi.org/10.1007/BF00427790

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