Reversal by L-Dopa of Impaired Learning Due to Destruction of the Dopaminergic Nigro-Neostriatal Projection
SciencePublished 13 September 1974
Athanasios P. Zis, Hans C. Fibiger, Anthony G. Phillips
Citations102
SJR quartileQ1
SJR score10.42
SNIP6.62
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
Abstract
Rats receiving bilateral stereotaxic injections of 6-hydroxydopamine into the zona compacta of the substantia nigra failed to learn a one-way active avoidance response. Small doses of L-dopa (1.5 milligrams per kilogram of body weight) in combination with a peripheral decarboxylase inhibitor reversed this impairment. Animals with lesions which acquired the avoidance response during L-dopa administration retained this response when drug treatment was discontinued. These experiments suggest that the dopaminergic nigro-neostriatal projection serves a critical function in the acquisition of learned instrumental responses.
Keywords
Neuroscience
Journal of Molecular MedicineVerteilung Von Noradrenalin Und Dopamin (3-Hydroxytyramin) Im Gehirn Des Menschen Und Ihr Verhalten Bei Erkrankungen Des Extrapyramidalen Systems
1,880 Citations1960H Ehringer, Oleh Hornykiewicz
The distribution of noradrenaline und dopamine (3-hydroxytyramine) in human adult and newborn brains has been investigated and the greatest amounts were found in the hypothalamus, the central gray matter of the mesencephalon, the reticular formation and in the area postrema.
New England Journal of MedicineAromatic Amino Acids and Modification of Parkinsonism
1,483 Citations1967George C. Cotzias, Melvin H. Van Woert +1 more
The interrelations between melanogenesis and extrapyramidal disease might be of fundamental importance and it was noted that chronic Parkinson's disease has a common precursor in the synthesis of both melanin and catecholamines.
Brain ResearchFeeding and drinking deficits after 6-hydroxydopamine administration in the rat: similarities to the lateral hypothalamic syndrome
292 Citations1973H.C. Fibiger, A.P. Zis +1 more
The results suggest that the lateral hypothalamic syndrome may to a large extent reflect the interruption of the dopaminergic nigro-striatal system and that other as yet unknown factors may also contribute to this syndrome.
ScienceImpaired Learning and Decreased Cortical Norepinephrine after Bilateral Locus Coeruleus Lesions
264 Citations1973Gill Anlezark, Timothy J. Crow +1 more
As assessed in this situation, learning was absent in those rats with the most complete ablations of the locus coeruleus, although these rats showed normal weight gain and normal motor and exploratory activity.
Brain ResearchA map of the rat mesencephalon for electrical self-stimulation
253 Citations1972Timothy J. Crow
It is proposed that the system of dopamine-containing neurones from the ventral mesencephalic tegmentum is one of two systems whose activation will support self-stimulattion responding.
Brain ResearchGrowth of central catecholamine neurones into smooth muscle grafts in the rat mesencephalon
233 Citations1971Anders Björklund, Ulf Stenevi
Brain ResearchIntracranial self-stimulation with electrodes in the region of the locus coeruleus
214 Citations1972Timothy J. Crow, P.J. Spear +1 more
It is proposed that the noradrenaline-containing system arising from the locus coeruleus is one of two neural systems which can be activated to obtain electrical self-stimulation, but the possibility that a fibre pathway associated with the mesencephalic root of the trigeminal nerve is involved cannot be excluded.
NeuropharmacologyTurning behavior of mice with unilateral 6-hydroxydopamine lesions in the striatum: Effects of apomorphine, l-DOPA, amantadine, amphetamine and other psychomotor stimulants
206 Citations1973P. F. VON VOIGTLANDER, Kenneth E. Moore
Turning behavior as performed in these experiments is a simple but very sensitive index of central dopaminergic receptor stimulation.
Journal of Pharmacology and Experimental TherapeuticsCEREBRAL ACCUMULATION AND METABOLISM OF C14-DOPA AFTER SELECTIVE INHIBITION OF PERIPHERAL DECARBOXYLASE
203 Citations1968G. Bartholini, A. Pletscher
It is concluded that Ro 4-4602 inhibits the decarboxylation of C 14 -dopa in extracerebral tissues rather selectively, which probably leads to an increased penetration of C 12 -dopamine from the blood into the brain, where it is then metabolized to C14 -catecholamines.
PubMedAlterations in behavior and brain catecholamine levels in rats treated with alpha-methyltyrosine.
202 Citations1966Richard H. Rech, H. K. Borys +1 more
ScienceDopaminergic and Noradrenergic Substrates of Positive Reinforcement: Differential Effects of <i>d</i> - and <i>l</i> -Amphetamine
197 Citations1973Anthony G. Phillips, Hans C. Fibiger
Intracranial self-stimulation data support the hypothesis that both dopaminergic and noradrenergic systems subserve positive reinforcement.
Canadian Journal of Biochemistry and PhysiologyCATECHOLAMINE CONTENT OF SPINAL CORD
161 Citations1962Edith G. McGeer, Patrick L. McGeer
Values for the catecholamine content of spinal cords of rats, rabbits, cats, humans, hogs, and oxen were obtained and dopamine and noradrenaline were both found in the free and bound state.
Pharmacology Biochemistry and BehaviorDeficits in instrumental responding after 6-hydroxydopamine lesions of the nigro-neostriatal dopaminergic projection
148 Citations1974H.C. Fibiger, Anthony G. Phillips +1 more
The results suggest that the nigro-neostriatal dopaminergic projection may play an important role in the acquisition of learned instrumental responses.
Journal of Pharmacology and Experimental TherapeuticsEFFECTS OF 6-HYDROXYDOPAMINE TREATMENTS ON ACTIVE AVOIDANCE RESPONDING: EVIDENCE FOR INVOLVEMENT OF BRAIN DOPAMINE
144 Citations1973Barrett R. Cooper, George R. Breese +2 more
The data suggest that the deficit in avoidance behavior observed in 6-OHDA-treated rats is due mainly to a reduction in brain dopamine and support the view that brain catecholamines are important for the maintenance of conditioned avoidance responding.
Brain ResearchBehavioral, biochemical, and histochemical analyses of the central effects of monoamine precursors after peripheral decar☐ylase inhibition
143 Citations1972Larry L. Butcher, Jörgen A. Engel +1 more
The histochemically assessed monoamine-depleting and behavioral suppressant effects of reserpine could be reversed by l -DOPA in rats given Ro 4-4602 and nialamide after the rauwolfia alkaloid.
HistochemieRegeneration of monoamine-containing axons in the developing and adult spinal cord of the rat following intraspinal 6-OH-dopamine injections or transections
120 Citations1971Lars Göran Nygren, Lars Olson +1 more
The present evidence suggests that reinnervation mainly is the result of downgrowth of the axotomized fibers, but growth in the form of collateral sprouting from a few possibly surviving fibers in the distal region may also contribute to a normal innervation pattern within 1–2 months in the various age groups.
British Journal of PharmacologyAttenuation of amphetamine‐induced motor stimulation and stereotypy by 6‐hydroxydopamine in the rat
116 Citations1973H.C. Fibiger, H. P. FIBIGER +1 more
The results are consistent with the view that amphetamine exerts its behavioural effects indirectly through its action on brain catecholamines and suggest that dopaminergic nigro‐striatal neurones mediate some of the stimulant effects of amphetamine as well as being of critical importance in amphetamine‐induced stereotypy.
PsychopharmacologyThe influence of various neuroleptic drugs on shock avoidance responding in rats
110 Citations1969C. J. E. Niemegeers, Frank Verbruggen +1 more
The effect of twenty neuroleptic drugs on conditioned behaviour was studied in rats by means of a lever-press shock-avoidance procedure and all drugs inhibited lever- press response and reduced the shock- avoidance rate at very low dose levels.
PsychopharmacologyTemporary and partial antagonism by l-DOPA of reserpine-induced suppression of a conditioned avoidance response
87 Citations1963Lewis S. Seiden, Arvid Carlsson
The suppression of the conditioned avoidance response induced by reserpine was partially and temporarily reversed by an injection of l-3,4-dihydroxyphenylalanine, and the suppression of locomotor activity was completely antagonized for approximately the same duration.
Journal of Pharmacy and PharmacologyDopa-induced locomotor stimulation after inhibition of extracerebral decarboxylase
77 Citations1969G. Bartholini, Johannes E. Blum +1 more
It is concluded that the locomotor activation after small doses of Ro 4–4602 in combination with dopa is due to cerebral accumulation of catecholamines which consist mainly of dopamine.
PsychopharmacologyReversal of the reserpine-induced suppression of the conditioned avoidance response in the cat by l-DOPA
65 Citations1964Lewis S. Seiden, Lennart C. F. Hanson
Summaryl-DOPA was effective in temporarily antagonizing the reserpine-induced suppression of a conditioned avoidance response and the effect was associated with the accumulation of dopamine in the brain.
Physiology & BehaviorEffect of central catecholamine alterations by 6-hydroxydopamine on shuttle box avoidance acquistion
61 Citations1972Barrett R. Cooper, George R. Breese +2 more
Rats treated intracisternally with multiple doses of 6-hydroxydopamine in combination with pargyline, which depleted both brain norepinephrine and dopamine, showed no evidence of acquisition of an avoidance response in the shuttle box.
Journal of Pharmacology and Experimental TherapeuticsENHANCEMENT BY 6-HYDROXYDOPAMINE OF THE EFFECTS OF DOPA UPON THE MOTOR ACTIVITY OF RATS
57 Citations1973Ronald I. Schoenfeld, Norman J. Uretsky
The results suggest that the enhanced effect of dopa in 6-HDA-treated rats is due to the production of a supersensitivity to catecholamines in the central nervous system of these animals.
Journal of Pharmacy and PharmacologyReversal of α-methyltyrosine-induced behavioural depression with dihydroxyphenylalanine and amphetamine
55 Citations1967Kenneth E. Moore, Richard H. Rech
Brain ResearchContrasting effects of hypothalamic and nucleus accumbens septi self-stimulation on brain stem single unit activity and cortical arousal
40 Citations1971Edmund T. Rolls
Very few brain stem single units were directly or synaptically excited through self-stimulation electrodes in the region of the nucleus accumbens septi, indicating that activation of a different neural system may mediate the rewarding effect of brain stimulation reward.
Physiology & BehaviorPotentiation of effects of L-dopa on conditioned avoidance behavior by inhibition of extracerebral dopa decarboxylase
23 Citations1971Lewis S. Seiden, Teackle W. Martin
The results indicate that extracerebral conversion of dopa to dopamine is not essential to the reversal of a reserpine-induced suppression of a conditioned avoidance response, and that there was a rise in brain levels of dopamine.