BEHAVIORAL-DIFFERENCES BETWEEN NEONATAL AND ADULT 6-HYDROXYDOPAMINE-TREATED RATS TO DOPAMINE AGONISTS - RELEVANCE TO NEUROLOGICAL SYMPTOMS IN CLINICAL SYNDROMES WITH REDUCED BRAIN DOPAMINE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 231  (2) , 343-354
Abstract
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 22-24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 m/kg), but did display paw treading and head nodding, behaviors not observed in neonatal 6-OHDA-treated rats. 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 G-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. Bisflupentixol completely blocked the SMB and self-biting induced by L-dopa. These behaviors in neonatal 6-OHDA-treated rats are apparently more associated with D-1 than D-2 receptor function. The age-dependent effects of dopamine agonists observed in these studies provide an explanation for the different symptomatology observed in Lesch-Nyhan patients and Parkinson''s disease, neurological disorders with reduced brain dopamine.