Modulation of avian muscarinic cholinergic high affinity binding sites by a neurotoxic organophosphate

A systematic survey of a series of high affinity binding sites in the forebrain of hens treated with a neurotoxic organophosphate has been carried out. Fourteen month old laying hens were treated with 750 mg/kg body weight triorthocresyl phosphate (TOCP) orally in gelatin capsules. Control birds received empty capsules. After 21 d, hens were killed and forebrain membrane fractions prepared for binding studies using the nitrocellulose filtration method. Incubations were carried out in the presence of low concentrations of pharmacological agents selective for certain classes of receptor sites. Nonspecific binding was characterized by simultaneous incubations in the presence of excess competing unlabeled ligands. Binding criteria that were satisfied in a prior study included specificity, saturability, and attainment of equilibrium during incubation. No significant change was found in treated hens assayed for dopaminergic, GABA, glycinergic, beta-adrenergic, and benzodiazepine receptors. However, a 30% reduction in binding of 3H-quinuclidinyl benzilate was apparent in TOCP-treated hens. These data implied a selective reduction of muscarinic receptors, suggesting a down-regulation in response to cholinergic hyperactivity. This dose of TOCP also caused paralysis and ataxia in all treated hens 21 d after exposure to the toxicant. These data demonstrate that a selective lesion in cholinergic neurotransmitter circuitry can be caused by a single administration of TOCP.