The involvement of alpha2-adrenoceptors in the anticonvulsive effect of swim stress in mice.
BACKGROUND
Various studies have shown that stressful manipulations in rats and mice lower the convulsant potency of GABA-related, but also some GABA-unrelated convulsants. The mechanism of this anticonvulsive effect of stress is still unknown.


OBJECTIVE
We tested the possible involvement of alpha2-adrenoceptors in the previously observed anticonvulsive effect of swim stress.


METHODS
The mice were, prior to exposure to swim stress and the IV infusion of picrotoxin, pre-treated with clonidine (an alpha2-adrenoceptor agonist), yohimbine (a non-selective alpha2-adrenoceptor antagonist), idazoxan (a selective alpha2-adrenoceptor antagonist), or niguldipine (an alpha1-adrenoceptor antagonist), and the latency to the onset of two convulsant signs was registered.


RESULTS
In control unstressed animals clonidine (0.1 and 1 mg/kg IP), yohimbine (2 mg/kg IP) and idazoxan (1 mg/kg IP) failed to affect the doses of picrotoxin needed to produce convulsant signs, while niguldipine (5 mg/kg IP) prolonged the latency, i.e. it enhanced the doses of picrotoxin producing running/bouncing clonus and tonic hindlimb extension. In swim stressed mice clonidine enhanced, while idazoxan decreased doses of picrotoxin needed to produce two convulsive signs. Yohimbine decreased the dose of convulsant needed to produce tonic hindlimb extension, while niguldipine enhanced doses of picrotoxin needed to produce both symptoms.


CONCLUSIONS
The results demonstrate the alpha2-adrenoceptor agonist-induced potentiation and alpha2-adrenoceptor antagonist-induced diminution of the anticonvulsive effect of stress. Additionally, they show the anticonvulsive effect of niguldipine in unstressed and stressed animals. Hence, the results suggest that alpha2-adrenoceptors are involved in the anticonvulsive effect of swim stress in mice.
Pericić
D
D
Laboratory for Molecular Neuropharmacology, Division of Molecular Medicine, Ruder Bosković Institute, P.O. Box 180, 10002 Zagreb, Croatia. pericic@rudjer.irb.hr
Svob
D
D
Jazvinsćak Jembrek
M
M
Mirković Kos
K
K
D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D003292:Convulsants / Q000008:administration & dosage / Q000009:adverse effects; D004095:Dihydropyridines / Q000008:administration & dosage; D058787:GABA-A Receptor Antagonists; D019329:Idazoxan / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010852:Picrotoxin / Q000008:administration & dosage / Q000009:adverse effects; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology*; D013550:Swimming
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D003292:Convulsants; D004095:Dihydropyridines; D058787:GABA-A Receptor Antagonists; D019329:Idazoxan; D010852:Picrotoxin; D018341:Receptors, Adrenergic, alpha-2; C054074:niguldipine