Evidence implicating alpha-2 adrenergic receptors in the anticonvulsant action of intranigral muscimol.
The effects of systemically administered catecholamine receptor antagonists on the anticonvulsant action produced by local application of a gamma-aminobutyric acid agonist, muscimol, to the substantia nigra of rats were studied. Both electroshock and kindled seizures were studied. Two alpha-2 receptor antagonists, idazoxan and yohimbine, blocked the anticonvulsant action of intranigral muscimol in the electroshock model. Neither a beta nor an alpha-1 adrenergic nor a dopamine-2 receptor antagonist blocked this action. In contrast to electroshock seizures, an alpha-2 antagonist only partially reversed the anticonvulsant action of intranigral muscimol in the kindling model. We interpret the data to indicate that the interaction of norepinephrine with alpha-2 receptors is required for the anticonvulsant action of intranigral muscimol in the electroshock model. The only partial reversal found in the kindling model suggests that nigral control of seizure propagation involves more than alpha-2 receptor mediated neurotransmission.
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D004146:Dioxanes / Q000627:therapeutic use; D019329:Idazoxan; D007696:Kindling, Neurologic; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy; D013378:Substantia Nigra / Q000187:drug effects
D000927:Anticonvulsants; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D009118:Muscimol; D019329:Idazoxan