Increased forebrain beta-adrenergic ligand binding induced by trimethyltin.
Systemic injection of the organometal neurotoxin trimethyltin (TMT) into rats causes impairments in learning and memory. However, there is a discontinuity in dose-response functions, such that the deficit which emerges with a higher, acutely toxic dose, is qualitatively different from the impairment induced after lower doses. To investigate synaptic receptor changes associated with behavioral deficits, neurotransmitter-receptor ligand binding assays were done in forebrain areas of rats given TMT (3.6 or 7.5 mg/kg). Binding of the beta-adrenergic ligand, dihydroalprenolol in frontal cortex and amygdala/pyriform cortex was an inverted U-shaped function of TMT dose, with rats given the median dose exhibiting increased binding. The curvilinear dose-response functions in behavioral and biochemical assays suggest that altered forebrain noradrenergic neurotransmission could play a role in behavioral deficits.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004082:Dihydroalprenolol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007858:Learning / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
D011942:Receptors, Adrenergic, alpha; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; D004082:Dihydroalprenolol