6-OHDA induced effects upon the acquisition and performance of specific locomotor tasks in rats

The effect of norepinephrine (NE) depletion on acquisition and performance of locomotor tasks requiring precise paw placement was tested. Running times (RT, 25 trials/day, 4 consecutive days) of water-deprived rats trained to transverse horizontal rods in an equally spaced regular rod arrangement (REG) were obtained before and after (REG/REG) intracisternal 6-hydroxydopamine (6-OHDA, 3 X 25 micrograms free base) infusion. No significant differences from ascorbate (0.1%) vehicle controls were seen. Additional rats were tested using the same protocol except a more difficult, irregularly spaced rod arrangement (IRR) was used. These IRR/IRR rats also revealed no significant differences. However, testing on the REG task before, and the new IRR task after infusion produced impaired performance on days 3 and 4 when 6-OHDA and vehicle treated rats were compared. These REG/IRR rats also showed a significant difference in the slope of the line reflecting the decrease in RT over the 4 day post-infusion period. Since no differences in intertrial intervals or extinction behavior were seen, the effect was not attributed to differences in arousal or motivational state. This effect could not be attributed to a simple reduction in non-specific activity, since significant differences in spontaneous locomotor activity or open field behavior were not seen. Assays verified the severe reduction of cerebellar NE to 14.5% of vehicle controls, and the smaller reduction in limbic forebrain NE and dopamine (53.8% and 75.2% of controls respectively). These findings suggest that NE deafferentation of the cerebellum causes impaired acquisition of locomotor behavior rather than an impairment of post-acquisitional performance.

[1]  P. Molinoff,et al.  Supersensitivity in rat cerebral cortex: pre- and postsynaptic effects of 6-hydroxydopamine at noradrenergic synapses. , 1977, Molecular pharmacology.

[2]  F. Bloom,et al.  Studies on norepinephrine-containing afferents to Purkinje cells of rat cerebellum. II. Sensitivity of Purkinje cells to norepinephrine and related substances administered by microiontophoresis. , 1971, Brain research.

[3]  Kety Ss.  The possible role of the adrenergic systems of the cortex in learning. , 1972 .

[4]  F. Bloom,et al.  Lesions of Central Norepinephrine Terminals with 6-OH-Dopamine: Biochemistry and Fine Structure , 1969, Science.

[5]  Donald J. Woodward,et al.  Potentiation of GABA inhibitory action in cerebellum by locus coeruleus stimulation , 1980, Brain Research.

[6]  S. T. Mason,et al.  Noradrenaline and avoidance learning in the rat , 1979, Brain Research.

[7]  G. Breese,et al.  Depletion of brain noradrenaline and dopamine by 6‐hydroxydopamine , 1971, British journal of pharmacology.

[8]  S. T. Mason,et al.  Locus coeruleus lesions: Learning and extinction , 1978, Physiology & Behavior.

[9]  G. Koob,et al.  Locus coeruleus lesions and learning in the rat , 1976, Physiology & Behavior.

[10]  K. Fuxe,et al.  On the projections from the locus coeruleus noradrealine neurons: the cerebellar innervation. , 1971, Brain research.

[11]  F. Bloom,et al.  Activation of the pathway from locus coeruleus to rat cerebellar Purkinje neurons: pharmacological evidence of noradrenergic central inhibition. , 1973, The Journal of pharmacology and experimental therapeutics.

[12]  T. Crow,et al.  Pontine tegmental lesions, monoamine neurons and varieties of learning. , 1977, Behavioral biology.

[13]  L. Stein,et al.  Memory enhancement by central administration of norepinephrine , 1975, Brain Research.

[14]  P. Jastreboff,et al.  A neuronal correlate in rabbit's cerebellum to adaptive modification of the vestibulo-ocular reflex , 1978, Brain Research.

[15]  B. Shaywitz,et al.  Simplified liquid chromatographic--electrochemical determination of norepinephrine and dopamine in rat brain. , 1980, Journal of chromatography.

[16]  D. Robinson.  Adaptive gain control of vestibuloocular reflex by the cerebellum. , 1976, Journal of neurophysiology.

[17]  R. Tallarida,et al.  Manual of Pharmacologic Calculations: With Computer Programs , 1984 .

[18]  J. Deakin,et al.  The locus coeruleus noradrenergic system — evidence against a role in attention, habituation, anxiety and motor activity , 1978, Brain Research.

[19]  T. Crow,et al.  Catecholamine-containing neurones and electrical self-stimulation: 2. A theoretical interpretation and some psychiatric implications , 1973, Psychological Medicine.

[20]  S. Iversen,et al.  The pharmacological and anatomical substrates of the amphetamine response in the rat , 1975, Brain Research.

[21]  Robert Freedman,et al.  Interactions of norepinephrine with Purkinje cell responses to putative amino acid neurotransmitters applied by microiontophoresis , 1979, Experimental Neurology.

[22]  T. Crow.  Cortical Synapses and Reinforcement: a Hypothesis , 1968, Nature.

[23]  N. Uretsky,et al.  Central effects of 6‐hydroxydopamine on the body temperature of the rat , 1970, British journal of pharmacology.

[24]  R. Mailman,et al.  Evaluation of the effects of nerve growth factor and anti-nerve growth factor on the development of central catecholamine-containing neurons , 1978, Brain Research.

[25]  F. A. Miles,et al.  Long-term adaptive changes in primate vestibuloocular reflex. IV. Electrophysiological observations in flocculus of adapted monkeys. , 1980, Journal of neurophysiology.

[26]  B. Culver,et al.  Measurement of the effects of drugs on activity of permanent groups of rats. , 1975, Psychopharmacology communications.

[27]  G. Breese,et al.  A biochemical and morphological study of the altered growth pattern of central catecholamine neurons following 6-hydroxydopamine , 1978, Brain Research.

[28]  Vicente Honrubia,et al.  Vestibular-ocular reflex in patients with lesions involving the vestibulocerebellum , 1981, Experimental Neurology.

[29]  D. Amaral,et al.  Locus coeruleus lesions and learning. , 1975, Science.

[30]  S. T. Mason,et al.  Learning in the absence of forebrain noradrenaline , 1975, Nature.

[31]  D. Puro,et al.  Interaction of norepinephrine with cerebellar activity evoked by mossy and climbing fibers , 1977, Experimental Neurology.

[32]  P. Gilbert.  How the cerebellum could memorise movements , 1975, Nature.

[33]  H. Fibiger,et al.  The dorsal tegmental noradrenergic projection: an analysis of its role in maze learning. , 1976, Journal of comparative and physiological psychology.

[34]  N. Uretsky,et al.  EFFECTS OF 6‐HYDROXYDOPAMINE ON CATECHOLAMINE CONTAINING NEURONES IN THE RAT BRAIN , 1970, Journal of neurochemistry.

[35]  P. Molinoff,et al.  beta-Adrenergic receptor involvement in 6-hydroxydopamine-induced supersensitivity in rat cerebral cortex. , 1976, Science.

[36]  J. Pettigrew,et al.  Restoration of visual cortical plasticity by local microperfusion of norepinephrine , 1979, The Journal of comparative neurology.

[37]  T. Ebner,et al.  Role of climbing fiber afferent input in determining responsiveness of Purkinje cells to mossy fiber inputs. , 1981, Journal of neurophysiology.

[38]  Masao Ito,et al.  The Cerebellar Modification of Rabbit's Horizontal Vestibulo-Ocular Reflex Induced by Sustained Head Rotation Combined with Visual Stimulation , 1974 .

[39]  U. Ungerstedt.  Stereotaxic mapping of the monoamine pathways in the rat brain. , 1971, Acta physiologica Scandinavica. Supplementum.

[40]  S. T. Mason,et al.  Effects of selective forebrain noradrenaline loss on behavioral inhibition in the rat. , 1977, Journal of comparative and physiological psychology.

[41]  R. Busto,et al.  Effects of noradrenaline depletion on adrenergic and muscarinic cholinergic receptors in the cerebral cortex, hippocampus, and cerebellum , 1981, Experimental Neurology.

[42]  S. Henriksen,et al.  Electrophysiology of purkinje neurons in the weaver mouse: Iontophoresis of neurotransmitters and cyclic nucleotides, and stimulation of the nucleus locus coeruleus , 1976, Brain Research.

[43]  G. Breese,et al.  Effect of 6-hydroxydopamine on brain norepinephrine and dopamine evidence for selective degeneration of catecholamine neurons. , 1970, The Journal of pharmacology and experimental therapeutics.

[44]  S. T. Mason,et al.  Reward, attention and the dorsal noradrenergic bundle , 1978, Brain Research.

[45]  A. Zis,et al.  Functional evidence for postsynaptic supersensitivity of central noradrenergic receptors after denervation , 1975, Nature.

[46]  P. Kissinger,et al.  DETERMINATION OF CATECHOLAMINES IN RAT BRAIN PARTS BY REVERSE‐PHASE ION‐PAIR LIQUID CHROMATOGRAPHY , 1978, Journal of neurochemistry.

[47]  S. T. Mason,et al.  An investigation of the role of cortical and cerebellar noradrenaline in associative motor learning in the rat , 1977, Brain Research.

[48]  F. Bloom,et al.  Spontaneous discharge of Purkinje neurons after destruction of catecholamine-containing afferents by 6-hydroxydopamine. , 1971, Brain research.

[49]  S. T. Mason,et al.  Evidence for a role of brain noradrenaline in attention and stimulus sampling , 1978, Brain Research.

[50]  T. Crow,et al.  Impaired Learning and Decreased Cortical Norepinephrine after Bilateral Locus Coeruleus Lesions , 1973, Science.

[51]  P. Gilbert.  A theory of memory that explains the function and structure of the cerebellum. , 1974, Brain research.

[52]  W. T. Thach,et al.  Purkinje cell activity during motor learning , 1977, Brain Research.