Neuropharmacological modification of central catecholamines: effects on pinealectomy-induced convulsions.
Removal of the pineal gland produces stereotyped tonic convulsions in parathyroidectomized rats. Inasmuch as central levels of norepinephrine (NE) are decreased in these animals, the purpose of this study was to investigate the effects of alterations in central catecholamine function on convulsions produced by pinealectomy in parathyroidectomized rats. The treatment of rats with alpha-methyl-p-tyrosine or FLA-63 produced large reductions in forebrain levels of both NE and dopamine or NE alone, respectively, which were not associated with facilitation of convulsions. However, the incidence of convulsions was increased by FLA-63 in rats pretreated with the catecholamine precursor L-dihydroxyphenylalanine. Reserpine, a monoamine depleter, had no effect on either the incidence or severity of convulsions. An acute injection of desipramine, an inhibitor of the reuptake of NE, however, significantly lowered the incidence of convulsions. Timolol, a beta-adrenergic receptor antagonist, reduced, in a dose-dependent manner, the average latency to onset of convulsions and increased the average number of convulsions each rat experienced. Clonidine, an alpha 2-adrenergic agonist, did not significantly alter convulsions. Thus presynaptic mechanisms such as synthesis and storage of both NE and DA appear to have little, if any, effect on pinealectomy-induced convulsions, whereas enhancing synaptic levels of NE by blocking its reuptake into adrenergic axons had an anticonvulsant effect. Further evidence suggesting a role for NE in modulating these convulsions is provided by the proconvulsant effect of blocking central beta-adrenergic receptors.
D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D002395:Catecholamines / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D010280:Parathyroid Glands / Q000502:physiology; D010870:Pineal Gland / Q000502:physiology*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D012640:Seizures / Q000503:physiopathology*; D013999:Timolol / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D007980:Levodopa; D019805:alpha-Methyltyrosine; D013999:Timolol; D012110:Reserpine; D003000:Clonidine; D003891:Desipramine