Limbic forebrain toxin trimethyltin reduces behavioral suppression by clonidine.
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.
Messing
R B
RB
Départment de Psychophysiologie, L.P.N.-C.N.R.S. Gif-sur-Yvette, France.
Devauges
V
V
Sara
S J
SJ
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*
D014298:Trimethyltin Compounds; D003000:Clonidine; D009638:Norepinephrine