Disordered dopamine neurotransmission in the striatum of rats undergoing pilocarpine-induced generalized seizures, as revealed by microdialysis.
In this study rats were fitted with a concentric dialysis probe in one striatum and extracellular concentrations of dopamine and HVA measured by reverse phase high performance liquid chromatography. Injections of saline or the D1 agonist SKF 38393 (30 mg/kg) did not affect the releases of these compounds. On the other hand, the D2 agonist LY 171555 (0.5 mg/kg) inhibited the release of both dopamine and HVA, whilst amphetamine (1 mg/kg) increased the output of dopamine but not HVA. Treatment with 200 mg/kg pilocarpine caused minimal signs of epileptic activity and did not affect striatal dopamine neurotransmission. Concomitant administration of SKF 38393 (30 mg/kg) to this dose of pilocarpine greatly facilitated the incidence and severity of motor seizures, which were accompanied by an irregular pattern of dopamine release and a significant rise in HVA overflow. Similar results were obtained with rats made to convulse with 400 mg/mg pilocarpine, and to a lesser extent if these animals were first pretreated with a protective dose of LY 171555 (0.5 mg/kg). It is concluded that dopamine neurotransmission in the striatum is disrupted in rats undergoing a pilocarpine-induced motor seizure, and that the extent of this disruption increases as the seizure becomes more severe. An irregular release of dopamine could signify a loss of sensorimotor control by the striatum, which might conceivably contribute to the intractability of the seizure. An increase in the dialysate concentrations of metabolite and not dopamine, is consistent with a heightened glutamate-stimulated release of dopamine from a discrete striatal pool, caused by the seizure spreading through the cortex and activating the cortico-striatal system.
al-Tajir
G
G
Department of Pharmacology, School of Pharmacy, London, United Kingdom.
Starr
M S
MS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000503:physiopathology*; D004873:Ergolines / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D010862:Pilocarpine; D019257:Quinpirole; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D015259:Dopamine Agents; D004873:Ergolines; D010862:Pilocarpine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000661:Amphetamine; D004298:Dopamine; D006719:Homovanillic Acid