title: Limbic forebrain toxin trimethyltin reduces behavioral suppression by clonidine.
abstract: Trimethyltin (TMT) at moderate doses selectively damages hippocampus and related olfactory cortex and produces learning and memory impairments. TMT also increases forebrain beta-adrenergic ligand binding; this could be ancillary to reduced noradrenergic neurotransmission, which in turn could be involved in the cognitive deficit caused by TMT. If this hypothesis is correct, then the alpha 1-adrenergic agonist clonidine, which inhibits noradrenergic neurotransmission in normal subjects, should be less behaviourally effective after TMT poisoning. Thus, rats treated with water vehicle or TMT (6 mg/kg, PO) were given saline or clonidine IP (5, 10, or 20 micrograms/kg) 30 min before placement in a hole-board apparatus. Exploratory activity was reduced in controls by 10 or 20 micrograms/kg. Clonidine at 10 micrograms/kg was ineffective in rats given TMT. At 20 micrograms/kg, an apparent reduction in exploratory activity was not significant because variability of responding was higher after TMT treatment. The results suggest an impairment in noradrenergic neurotransmission following TMT poisoning.
authors.affiliation: Départment de Psychophysiologie, L.P.N.-C.N.R.S. Gif-sur-Yvette, France.
authors.forename: R B
authors.initials: RB
authors.lastname: Messing
authors.forename: V
authors.initials: V
authors.lastname: Devauges
authors.forename: S J
authors.initials: SJ
authors.lastname: Sara
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D008032:Limbic System / Q000187:drug effects*; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects*; D051381:Rats; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D014298:Trimethyltin Compounds; D003000:Clonidine; D009638:Norepinephrine