Functional changes induced by neonatal cerebral 6-hydroxydopamine treatment: effects of dose levels on behavioral parameters. 1997

J Luthman, and M Bassen, and A Fredriksson, and T Archer
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.

Male Sprague-Dawley rats were treated neonatally with either of three different doses of 6-hydroxydopamine (6-OHDA): 50 micrograms i.c., 75 micrograms i.c., or 2 x 100 micrograms i.c.v., 30 min after a subcutaneous injection of desipramine (DMI, 25 mg/kg), in order to obtain selective lesions of mesencephalic dopamine (DA) neurons to different extents. From juvenile ages onwards, rats in each dose condition were tested for spontaneous motor activity and exploration in an openfield/holeboard setting measuring ambulation, rearing and head-dips. Between 77 and 78 days, the animals were tested in a modified, enclosed radial arm maze, followed 1 week later by tests in the circular swim maze. Finally, motor activity was tested in automated activity test chambers. In the openfield/holeboard setting, hyperactivity was seen for both rearing and ambulation in rats administered 50 micrograms 6-OHDA, whereas the 75 micrograms and 2 x 100 micrograms groups showed hyperactivity for ambulation, but hypoactivity for rearing and head-dips. All three dose groups demonstrated a retardation of learning in the radial arm maze. The 75 and 2 x 100 micrograms groups, but not the 50 micrograms group, showed impairments of acquisition in the swim maze. In the activity test chambers locomotion and rearing behavior varied as a function of 6-OHDA dose, being negatively and positively, respectively, related to DA concentration in striatum. These results show that the extent of the neonatal DA lesion determines both changes in motor- and exploratory activity as well as the occurrence and severity of acquisition impairment in spatial learning tasks.

UI MeSH Term Description Entries
D007267 Injections Introduction of substances into the body using a needle and syringe. Injectables,Injectable,Injection
D007276 Injections, Intraventricular Injections into the cerebral ventricles. Intraventricular Injections,Injection, Intraventricular,Intraventricular Injection
D008297 Male Males
D008636 Mesencephalon The middle of the three primitive cerebral vesicles of the embryonic brain. Without further subdivision, midbrain develops into a short, constricted portion connecting the PONS and the DIENCEPHALON. Midbrain contains two major parts, the dorsal TECTUM MESENCEPHALI and the ventral TEGMENTUM MESENCEPHALI, housing components of auditory, visual, and other sensorimoter systems. Midbrain,Mesencephalons,Midbrains
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D002946 Cisterna Magna One of three principal openings in the SUBARACHNOID SPACE. They are also known as cerebellomedullary cistern, and collectively as cisterns. Magna, Cisterna
D003891 Desipramine A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. Desmethylimipramine,Apo-Desipramine,Demethylimipramine,Desipramine Hydrochloride,Norpramin,Novo-Desipramine,Nu-Desipramine,PMS-Desipramine,Pertofran,Pertofrane,Pertrofran,Petylyl,Ratio-Desipramine,Apo Desipramine,Hydrochloride, Desipramine,Novo Desipramine,Nu Desipramine,PMS Desipramine,Ratio Desipramine
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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