Document Detail

Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine.
MedLine Citation:
PMID:  6149306     Owner:  NLM     Status:  MEDLINE    
Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding--behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-beta-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High doses of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa.(ABSTRACT TRUNCATED AT 400 WORDS)
G R Breese; A A Baumeister; T J McCown; S G Emerick; G D Frye; K Crotty; R A Mueller
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  231     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1984 Nov 
Date Detail:
Created Date:  1984-12-19     Completed Date:  1984-12-19     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  343-54     Citation Subset:  IM    
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MeSH Terms
Age Factors
Antipsychotic Agents / pharmacology
Behavior, Animal / drug effects*
Brain Chemistry / drug effects*
Dopa Decarboxylase / antagonists & inhibitors
Dopamine / analysis*
Dopamine beta-Hydroxylase / antagonists & inhibitors
Dose-Response Relationship, Drug
Hydroxydopamines / toxicity*
Lesch-Nyhan Syndrome / etiology*
Levodopa / pharmacology
Motor Activity / drug effects
Norepinephrine / analysis
Parkinson Disease, Secondary / etiology*
Rats, Inbred Strains
Receptors, Dopamine / drug effects*
Serotonin / analysis
Grant Support
Reg. No./Substance:
0/Antipsychotic Agents; 0/Hydroxydopamines; 0/Receptors, Dopamine; 333DO1RDJY/Serotonin; 46627O600J/Levodopa; 8HW4YBZ748/Oxidopamine; EC beta-Hydroxylase; EC 4.1.1.-/Dopa Decarboxylase; VTD58H1Z2X/Dopamine; X4W3ENH1CV/Norepinephrine

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