Dose-related effects of a neonatal 6-OHDA lesion on SKF 38393- and m-chlorophenylpiperazine-induced oral activity responses of rats

• Published in: Brain research. Developmental brain research Vol. 76; no. 2; pp. 233 - 238
• Main Authors: Gong, Li, Kostrzewa, Richard M., Perry, Ken W., Fuller, Ray W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 17.12.1993; Elsevier
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology; 6-Hydroxydopamine; Animals; Biogenic Monoamines - metabolism; Biological and medical sciences; Corpus Striatum - metabolism; Development. Senescence. Regeneration. Transplantation; Dopamine; Dopamine D 1 receptor; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; m-Chlorophenylpiperazine; Mouth; Movement - drug effects; Ontogeny; Oral activity; Oxidopamine; Piperazines - pharmacology; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin receptor; Serotonin Receptor Agonists - pharmacology; SKF 38393; Supersensitization; Vertebrates: nervous system and sense organs; Dopamine; Serotonin; SKF 38393; Serotonin receptor; Oral activity; 6-Hydroxydopamine; Dopamine D 1 receptor; Ontogeny; Supersensitization; m-Chlorophenylpiperazine; Jaw; Serotoninergic receptor; Rat; Rodentia; Central nervous system; D1 Dopamine receptor; Basal ganglion; Corpus striatum; Oxidopamine; Postnatal development; Dose activity relation; Vertebrata; Mammalia; Body movement; Lesion; Brain (vertebrata)
• ISSN: 0165-3806
• DOI: 10.1016/0165-3806(93)90211-R

Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with concurrent supersensitization of dopamine (DA) D 1 and serotonin 5-HT 1C receptors, for agonist-induced oral activity. The present study was conducted to determine if graded reduction of striatal DA content and/or graded elevation of striatal 5-HT content by 6-OHDA would alter sensitivity of either receptor type, and thereby influence oral activity responses to DA and 5-HT agonists. At 3 days after birth, groups of rats were pretreated with desipramine (20 mg/kg i.p.), 1 h before administration of a range of doses of 6-OHDA HBr (15, 30, 60, 100, 150 and 200 μg, i.c.v., salt form; half in each lateral ventricle) or the vehicle, saline (0.85%)-ascorbic acid (0.1%). Between 2 and 4 months, a series of challenge doses of SKF 38393 HCl (0.30 to 3.0 mg/kg i.p.) and m-chlorophenylpiperazine 2HCl (0.30 to 6.0 mg/kg i.p.; m-CPP 2HCl) were administered to each group of rats and oral activity was observed. Oral activity was determined for 1 min every 10 min during a 60-min period, starting 10 min after injection of agonist or vehicle. SKF 38393 dose-response curves demonstrated enhanced oral activity responses in rats lesioned neonatally with 150 or 200 μg of 6-OHDA. m-CPP dose-response curves demonstrated enhanced oral activity responses in these 2 groups of rats, as well as those lesioned neonatally with 100 μg of 6-OHDA. Striatal DA content was reduced by > 97% in these 3 groups of rats. Striatal 5-HT content was elevated by > 80% in rats treated neonatally with 150- or 200-μg doses of 6-OHDA, and by 50% in rats treated neonatally with the 100-μg dose of 6-OHDA. Lower doses of 6-OHDA produced less of an effect on striatal DA and 5-HT content. Regression analysis determined that both SKF 38393- and m-CPP-induced oral activities were most closely correlated with the magnitude of change in striatal content of DA. These findings demonstrate that 5-HT agonist responses can be enhanced when DA agonist responses are not enhanced. Also, in neonatal 6-OHDA-lesioned rats the extent of DA depletion vs. the extent of 5-HT elevation seems to be a critical factor in the enhanced behavioral effects of DA and 5-HT agonists.