Abstract
The relative contribution of dopamine (DA) and norepinephrine (NE) in behavioral arousal was examined in developing rat pups using intracisternal 6-hydroxydopamine (6-OHDA) either alone or following pretreatment with desmethylimipramine (DMI). Such treatments were designed to examine the effects of preferential reduction of DA (DA depletion), NE (NE depletion), or both catecholamines (CA depletion) in the development of motor activity and escape performance. General motor activity increased with age and, over all ages, DA-depleted pups tended to exhibit greater activity. This was most apparent at 15 days of age, where DA-depleted pups were significantly more active than controls, NE-depleted, or CA-depleted pups. DA-depleted pups failed to exhibit the steep decline in activity over time (habituation of activity) demonstrated by the control and NE-depleted pups, while pups depleted of both CA fell into an intermediate position in habituation. Escape latency in a T-maze at 20 days and shuttle box at 26 days of age indicated comparable performance to controls for NE-depleted pups, while those animals in DA-depleted and CA-depleted groups appeared unable to perform the task. Brain CA concentrations (determined by a radioenzymatic assay) indicated preferential reduction of DA in the DA-depleted group to concentrations 25% of controls, reduction of NE to 62% of controls in the NE-depleted group, and reductions of DA to 42% and NE to 60% in the CA-depleted group. These results suggest that preferential reduction of brain DA in the developing rat pup increases motor activity and impairs habituation of activity during the stage of behavioral arousal in week 3 of postnatal life. A theory incorporating both NE facilitory mechanisms and pre- and postsynaptic dopaminergic mechanisms in the mesolimbic-dopaminergic pathway is proposed.
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References
Antelman SM, Caggiula AR (1977) Norepinephrine-dopamine interactions and behavior. Science 195:646–653
Axelrod J, Tomchick R (1958) Enzymatic O-methylation of epinephrine and other catechols. J Biol Chem 233:702–705
Breese GR, Traylor TD (1972) Developmental characteristics of brain catecholamines and tyrosine hydroxylase in the rat: Effects of 6-OHDA. Br J Pharmacol 44:210–222
Breese GR, Smith RD, Cooper BR (1975) Effect of various 6-hydroxydopamine treatments during development on growth and ingestive behavior. Pharmacol Biochem Behav 3:1097–1106
Bruning JL, Kintz BL (1977) Computational handbook of statistics. Scott, Foresman, Glenview, IL, pp 18–92
Campbell BA, Mabry PD (1973) The role of catecholamines in behavioral arousal during ontogenesis. Psychopharmacologia 31:253–264
Carter CJ, Pycock CJ (1980) Behavioural and biochemical effects of dopamine and noradrenaline depletion within the medial prefrontal cortex of the rat. Brain Res 192:163–176
Cooper JR, Bloom FE, Roth RH (1982) The biochemical basis of neuropharmacology. Oxford University Press, New York, pp 109–221
Costall B, Fortune DH, Hui SG, Naylor RJ (1980) Neuroleptic antagonism of the motor inhibitory effects of apomorphine within the nucleus accumbens: Drug interaction at presynaptic receptors. Eur J Pharmacol 63:347–358
Coyle JT (1974) Biochemical aspects of the catecholaminergic neurons in the brain of the fetal and neonatal rat. In: Fuxe K, Olson L, Zotterman Y (eds) Dynamics of degeneration and growth in neurons. Pergamon, Oxford, pp 425–434
Coyle JT, Henry D (1973) Catecholamines in fetal and newborn rat brain. J Neurochem 21:61–67
Dunn OJ (1961) Multiple comparisons among means. J Am Stat Assoc 56:52
Erinoff L, MacPhail RC, Heller A, Seiden LS (1979) Age-dependent effects of 6-hydroxydopamine on locomotor activity in the rat. Brain Res 164:195–205
Glowinski J, Axelrod J, Iverson LL (1966) Regional studies of catecholamines in the rat brain. 4. Effects of drugs on the disposition and metabolism of 3H-norepinephrine and 3H-dopamine. J Pharmacol Exp Ther 153:30–41
Goodale DB, Rusterholz DB, Long JP, Flynn JR, Walsh B, Cannon JG, Lee T (1980) Neurochemical and behavioral evidence for a selective presynaptic dopamine receptor agonist. Science 210:1141–1143
Heffner T, Miller F, Kotake C, Heller A, Seiden L (1980) Transient or permanent hyperactivity following neonatal 6-hydroxydopamine: A function of brain dopamine depletion. Soc Neurosci Abstr 6:108
Jonsson G, Sachs C (1973) Pharmacological modifications of the 6-hydroxy-dopa-induced degeneration of central noradrenaline neurons. Biochem Pharmacol 22:1709–1716
Shaywitz BA, Yager RD, Klopper JH (1976a) Selective brain dopamine depletion in developing rats: An experimental model of minimal brain dysfunction. Science 191:305–308
Shaywitz BA, Klopper JH, Yager RD, Gordon JW (1976b) Paradoxical response to amphetamine in developing rats treated with 6-hydroxydopamine. Nature 261:153–155
Shaywitz BA, Gordon JW, Klopper JH, Zelterman D (1977) The effect of 6-hydroxydopamine on habituation of activity in the developing rat pup. Pharmacol Biochem Behav 6:391–396
Shaywitz BA, Pearson DE (1978) Effects of phenobarbital on activity and learning in 6-hydroxydopamine-treated rat pups. Pharmacol Biochem Behav 9:173–180
Shaywitz BA, Klopper JH, Gordon JW (1978) Methylphenidate in 6-hydroxydopamine-treated developing rat pups. Arch Neurol 35:463–469
Shaywitz BA, Yager RD, Gordon JW (1979) Ontogeny of brain catecholamine turnover and susceptibility to audiogenic seizures in DBA/2j mice. Dev Psychobiol 11:243–250
Shaywitz SE, Shaywitz BA, Cohen DJ, Young JG (1983) Monoaminergic mechanisms in hyperactivity. In: Rutter M (ed) Developmental neuropsychiatry. Guilford Press, New York, pp 330–347
Smith RD, Cooper BR, Breese GR (1973) Growth and behavioral changes in developing rats treated intracisternally with 6-hydroxydopamine: Evidence for involvement of brain dopamine. J Pharmacol Exp Ther 185:609–619
Stoof JC, Dijkstra H, Hillegers JPM (1978) Changes in the behavioral response to a novel environment following lesioning of the central dopaminergic system in rat pups. Psychopharmacology 57:163–166
Tassin JP, Stinus L, Simon H, Blanc G, Thierry AM, LeMoal M, Cardo B, Glowinski J (1978) Relationship between the locomotor hyperactivity induced by A-10 lesions and the destruction of the frontocortical dopaminergic innervation in the rat. Brain Res 141:267–281
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Shaywitz, B.A., Teicher, M.H., Cohen, D.J. et al. Dopaminergic but not noradrenergic mediation of hyperactivity and performance deficits in the developing rat pup. Psychopharmacology 82, 73–77 (1983). https://doi.org/10.1007/BF00426384
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DOI: https://doi.org/10.1007/BF00426384