Abstract
To examine the possible involvement of the norepinephrine (NE) containing neurons of the locus coeruleus in the modulation of behavioral reactivity to sensory stimulation, bilateral chemical lesions of the locus coeruleus were made by local injection of the catecholamine neurotoxin 6-hydroxydopamine. Both histochemical and biochemical analyses confirmed the effectiveness of the lesions in specifically eliminating the NE containing cell bodies of the locus coeruleus and reducing the NE content of the hippocampus and substantia nigra by 45% and 69% respectively. Rats were tested both 5 and 36 days after lesioning for their startle response to a repetitive series of tactile stimuli. On both days, locus coeruleus lesioned rats exhibited consistently reduced startle responses throughout the stimulus series. Additionally, lesioned rats showed a far more rapid rate of response habituation, particularly in the first test. The results are discussed in terms of a possible influence of the locus coeruleus on the process of sensitization to sensory stimuli.
Similar content being viewed by others
References
Cedarbaum JM, Aghajanian GK (1979) Activation of locus coeruleus noradrenergic neurons by peripheral nerve stimulation. Neurosci Abstr 3:769
Coyle JT, Henry D (1973) Catecholamines in fetal and newborn rat brain. J Neurochem 2:61–68
Davis M, Cedarbaum JM, Aghajanian GK, Gendelman DS (1977) Effects of clonidine on habituation and sensitization of acoustic startle in normal, decerebrate and locus coeruleus lesioned rats. Psychopharmacology 51:243–253
Davis M, Svensson T, Aghajanian G (1975) Effects of d- and l-amphetamine on habituation and sensitization of the acoustic startle response in rats. Psychopharmacology 43:1–11
Fechter LD (1974) The effects of L-dopa, clonidine, and apomorphine on the acoustic startle reaction in rats. Psychopharmacologia 39:331–344
Foote SL, Bloom FE (1978) Activity of norepinephrine-containing locus coeruleus neurons in the unanesthesized squirrel monkey. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: Basic and clinical frontiers, Vol. I Pergamon Press, New York, pp 625–630
Geyer MA (1978) Heterogenous functions of discrete serotonergic pathways in brain. In: Usdin E, Mandell AJ (eds) New vistas in the biochemistry of mental disorders, Vol. 13. Marcel Dekker Inc., New York, pp 233–257
Geyer MA, Dawsey WJ, Mandell AJ (1978b) Fading: A new cytofluorimetric measure quantifying serotonin in the presence of catecholamines at the cellular level in brain. J Pharmacol Exp Ther 207:650–667
Geyer MA, Petersen LR, Rose GJ, Horwitt DD, Light RK, Adams LM, Zook JA, Hawkins RL, Mandell AJ (1978a) The effects of lysergic acid diethylamide and mescaline-derived hallucinogens on sensory-integrative function: tactile startle. J Pharmacol Exp Ther 207:837–847
Groves PM, Thompson RF (1970) Habituation: A dual process theory. Psychol Rev 77:419–450
Handley SL, Thomas KV (1979) Potentiation of startle response by d- and l-amphetamine: The possible involvement of pre- and postsynaptic alpha-adrenoreceptors and other transmitter systems in the modulation of a tactile startle response. Psychopharmacology 64:105–111
Jones G, Segal M, Bloom F (1978) Locus coeruleus neurons in freely moving rats exhibit pronounced alterations of discharge rate during sensory stimulation and stages of the sleep-wake cycle. In: Usdin E, Kopin IJ, Barchas J (eds) Catecholamines: basic and clinical frontiers, Vol. 1. Pergamon Press, pp 643–645
Kehne JH, Sorenson CA (1978) The effects of pimozide and phenoxybenzamine pretreatments on amphetamine and apomorphine potentiation of the acoustic startle response in rats. Psychopharmacology 58:137–144
Kirkby R, Bell D, Preston A (1972) The effects of methylamphetamine on stereotyped behaviour, activity, startle, and orienting responses. Psychopharmacologia 25:41–48
Kokkinidis L, Anisman H (1978) Involvement of norepinephrine in startle arousal after acute and chronic d-amphetamine administration. Psychopharmacology 59:285–292
Loughlin SE, Foote SL, Bloom FE (1979) Topographic organization of constituent neurons. Neurosci Abstr 5:1136
Loy R, Moore RY (1979) Ontogeny of the noradrenergic innervation of the rat hippocampal formation. Anat Embryol (Berl) 157:243–253
Nakai Y, Takahori S (1974) Influence of norepinephrine-containing neurons derived from the locus coeruleus on lateral geniculate neuronal activity of cats. Brain Res 71:47–60
Nygren L, Olson L (1977) A new major projection from locus coeruleus: The main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord. Brain Res 132:85–93
Olson L, Fuxe K (1971) On the projections from the locus coeruleus noradrenalin neurons: the cerebellar innervation. Brain Res 28:167–177
Pickel VM, Segal M, Bloom FE (1974) A radioautographic study of the efferent pathways of the nucleus locus coeruleus. J Comp Neurol 155:15–42
Redmond DE, Jr (1977) Alterations in the function of the nucleus locus coeruleus: a possible model for studies of anxiety. In: Hanin I, Usdin E (eds) Animal models in psychiatry and neurology, Pergamon Press, Oxford, pp 293–304
Roberts DCS, McCaughran JA, Jr, Fibiger HC (1979) Behavioural effects of 6-hydroxydopamine-induced depletion of spinal noradrenaline. Can J Physiol Pharmacol 57:1223–1228
Segal M, Bloom FE (1969) The action of norepinephrine in the rat hippocampus IV. The effects of locus coeruleus stimulation on evoked hippocampal unit activity. Brain Res 107:513–525
Segal M, Bloom FE (1976b) The action of norepinephrine in rat hippocampus III. Hippocampal cellular responses to locus coeruleus stimulation in the awake rat. Brain Res 107:499–511
Segal M, Bloom FE (1974) The action of norepinephrine in rat hippocampus. II. Activation of the input pathway. Brain Res 107:99–114
Sorenson CA, Davis M (1975) Effects of 6-hydroxydopamine and alphamethyl-para-tyrosine on the acoustic startle response in rats. Pharmacol Biochem Behav 3:325–329
Svensson T, Bunney B, Aghajanian G (1975) Inhibition of both noradrenergic and serotonergic neurons in brain by the alphaadrenergic agonist clonidine. Brain Res 92:291–306
Szabo I (1964) Analysis of the muscular action potentials accompanying the acoustic startle reaction. Acta Physiol Hung 27:167–178
Thompson RF, Groves PM, Teyler TJ, Roemer RA (1973) A dual process theory of habituation: theory and behavior. In: Peeke HVS, Herz MJ (eds). Habituation, Vol I. Academic Press, New York, London, pp 239–271
Ungerstedt U (1971) Stereotaxic mapping of the monoamine pathways in the rat brain. Acta Physiol Scand (Suppl) 367:1–48
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Adams, L.M., Geyer, M.A. Effects of 6-hydroxydopamine lesions of locus coeruleus on startle in rats. Psychopharmacology 73, 394–398 (1981). https://doi.org/10.1007/BF00426474
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00426474