Regional changes in brain dopamine utilization during status epilepticus in the rat induced by systemic pilocarpine and intrahippocampal carbachol.
Systemic administration of pilocarpine (400 mg/kg i.p.) or intrahippocampal injection of carbachol (100 micrograms/1 microliters) induced limbic motor seizures in rats, characterized by head weaving and paw treading, rearing and falling, and forepaw myoclonus, developing into status epilepticus. After being in status for 30 min, rats were killed and levels of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined in eight brain regions by high performance liquid chromatography. Pilocarpine-induced seizures significantly elevated dopamine in the striatum, and in both dorsal and ventral aspects of the hippocampus, but did not affect dopamine in substantia nigra, nucleus accumbens, olfactory tubercle, cingulate cortex or amygdala. Metabolite levels were increased in striatum, substantia, nigra, nucleus accumbens and cingulate cortex, and fell in the hippocampus, but remained unchanged in the olfactory tubercle and amygdala. Intrahippocampal carbachol significantly raised the dopamine contents of striatum and nigra, and in both ventral and dorsal aspects of the hippocampus, but not elsewhere. DOPAC and/or HVA were elevated in all brain regions tested, save for amygdala and dorsal hippocampus. These changes translated into seizure-induced increases in dopamine utilization in the nucleus accumbens, olfactory tubercle and cingulate cortex, and to a fall in dopamine utilisation in the hippocampus, with no net change in amygdala. In addition pilocarpine (but not carbachol) increased dopamine utilization in the nigrostriatal axis, possibly through a seizure-unrelated mechanism. The relevance of these findings to seizure development are discussed.
Alam
A M
AM
Department of Pharmacology, School of Pharmacy, London, U.K.
Starr
M S
MS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002217:Carbachol; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology*; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
D018721:Muscarinic Agonists; D010862:Pilocarpine; D015102:3,4-Dihydroxyphenylacetic Acid; D002217:Carbachol; D004298:Dopamine; D006719:Homovanillic Acid