Modulation of audiogenic seizures by histamine and adenosine receptors in the inferior colliculus.
Susceptibility to behaviorally similar audiogenic seizures (AGS) occurs genetically and is inducible during ethanol withdrawal (ETX). Comparisons between AGS mechanisms of genetically epilepsy-prone rats (GEPR-9s) and ethanol-withdrawn rats (ETX-Rs) are yielding information about general pathophysiological mechanisms of epileptogenesis. The inferior colliculus (IC) is the AGS initiation site. Excitatory amino acid (EAA) abnormalities in the IC are implicated in AGS, and histamine and adenosine receptor activation each reduce EAA release and inhibit several seizure types. Previous studies indicate that focal infusion of an adenosine receptor agonist into the IC blocked AGS in GEPR-9s, but the effects of adenosine receptor activation in the IC on AGS in ETX-Rs are unknown. The effects of histamine receptor activation on either form of AGS are also unexamined. The present study evaluated effects of histamine or a nonselective adenosine A(1) agonist, 2-chloroadenosine, on AGS by focal microinjection into the IC. Ethanol dependence and AGS susceptibility were induced in normal rats by intragastric ethanol. Histamine (40 or 60 nmol/side) significantly reduced AGS in GEPR-9s, but histamine in doses up to 120 nmol/side did not affect AGS in ETX-Rs. 2-Chloroadenosine (5 or 10 nmol/side) did not affect AGS in ETX-Rs, despite the effectiveness of lower doses of this agent in GEPR-9s reported previously. Thus, histamine and adenosine receptors in the IC modulate AGS of GEPR-9s, but do not modulate ETX-induced AGS. The reasons for this difference may involve the chronicity of AGS susceptibility in GEPR-9s, which may lead to more extensive neuromodulation as compensatory mechanisms to limit the seizures compared to the acute AGS of ETX-Rs.
Feng
H J
HJ
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9629, USA.
Faingold
C L
CL
D015762:2-Chloroadenosine / Q000008:administration & dosage / Q000494:pharmacology*; D000161:Acoustic Stimulation; D020270:Alcohol Withdrawal Seizures / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D020195:Epilepsy, Reflex / Q000188:drug therapy* / Q000378:metabolism; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D007245:Inferior Colliculi / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008845:Microinjections; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley
D058906:Purinergic P1 Receptor Agonists; D015762:2-Chloroadenosine; D006632:Histamine