Kindled seizures do not affect adenosinergic inhibition of DA or ACh release in rat accumbens or PFC.
Epileptic seizures are thought to terminate largely as a result of the extracellular accumulation of the purinergic neuromodulator, adenosine, released by discharging neurons. However, the postictal surge in extracellular adenosine and its widespread inhibitory effects are limited in time to only a few minutes and cannot directly account for increased resistance to seizures and the complex behavioural and motivational effects that may persist for hours or days after a seizure. The present study examined whether kindled seizures might alter the sensitivity or efficacy of inhibitory presynaptic adenosine receptors, and thereby induce more enduring changes in downstream transmitter systems. Rats were kindled in the amygdala of the dominant cerebral hemisphere, contralateral to the preferred direction of rotation, and their brains were removed either 2 h or 28 days after completion of kindling. Inhibition of electrically stimulated release of dopamine (DA) and acetylcholine (ACh) by the A1 adenosine-receptor agonist, R-phenylisopropyladenosine (R-PIA) was then measured in the prefrontal cortex (PFC) and nucleus accumbens. R-PIA (1.0 microM) inhibited [1H]DA release from PFC and nucleus accumbens tissue, and [14C]ACh release from nucleus accumbens tissue, but release was unaffected by prior kindling, regardless of the intervening interval. These results do not support suggestions that DA or ACh might mediate the effects of seizure-induced changes in purinergic inhibitory tone so as to cause long-term shifts in seizure threshold and postictal behavior.
Engelbrecht
A H
AH
Department of Chemical Pathology, University of Stellenbosch, Tygerberg Hospital, South Africa.
Russell
V A
VA
Mintz
M
M
Lamm
M C
MC
Kellaway
L
L
Herberg
L J
LJ
Taljaard
J J
JJ
D000109:Acetylcholine / Q000037:antagonists & inhibitors*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007696:Kindling, Neurologic; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D012640:Seizures / Q000503:physiopathology*
D058906:Purinergic P1 Receptor Agonists; D010660:Phenylisopropyladenosine; D000109:Acetylcholine; D004298:Dopamine