title: Endosulfan induces small but significant changes in the levels of noradrenaline, dopamine and serotonin in the developing rat brain and deficits in the operant learning performance.
abstract: The organochlorine insecticide, endosulfan was administered (6 mg/kg body weight) to Wistar rat pups of both sexes by gastric intubation daily from post-natal days 2-25. Its effect on levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) was assayed in olfactory bulb (OB), hippocampus (HI), visual cortex (VC), brainstem (BS) and cerebellum (CB) on days 10 and 25 using high-performance liquid chromatography (HPLC). The activity of acetylcholinesterase (AChE) was also estimated in the same regions of the brain. Performance in operant conditioning for solid food reward was assessed in 25-day-old rats. NA levels were increased in OB (12%, P < 0.01) and BS (10%, P < 0.05) at 10 days of age and in HI (20%, P < 0.01) and CB (12%, P < 0.05) at 25 days of age. DA level was decreased in HI at both 10 (42%, P < 0.001) and 25 (45%, P < 0.001) days. Serotonin levels were increased in OB (12%, P < 0.05), HI (41%, P < 0.001), VC (30%, P < 0.01) and BS (15%, P < 0.01) at 10 days of age but at 25 days, levels were decreased in BS (20%, P < 0.05) and CB (31%, P < 0.01). The activity of AChE was not different from the control groups in any of the regions studied. These data suggest that monoaminergic systems in the developing rat brain respond to endosulfan by undergoing something like a 'reorganization'. However, such changes do not ameliorate certain functional losses following the exposure to endosulfan as operant conditioning revealed deficits in acquisition as well as retention of memory.
authors.affiliation: Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
authors.forename: M K
authors.initials: MK
authors.lastname: Lakshmana
authors.forename: T R
authors.initials: TR
authors.lastname: Raju
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D004726:Endosulfan / Q000633:toxicity*; D005260:Female; D008297:Male; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D012701:Serotonin; D000110:Acetylcholinesterase; D000254:Sodium-Potassium-Exchanging ATPase; D004726:Endosulfan; D004298:Dopamine; D009638:Norepinephrine