Phencyclidine prevents spatial navigation and passive avoidance deficits in ibotenate lesioned rats.
The potential neuroprotective effects of phencyclidine (5 mg/kg i.p.) were assessed in rats which had been treated with the excitotoxin, ibotenic acid (IBO) (0.015 M) to lesion the nucleus basalis magnocellularis. IBO treated rats showed a significant impairment in 13 of the 25 test trials in the spatial navigation Morris water maze task and deficits in passive avoidance learning. Phencyclidine was found to prevent the IBO-induced impairment in 4 of the 13 test trials in which the IBO Morris maze deficit was observed and also successfully prevented the passive avoidance learning deficits. Neurochemically, IBO was shown to reduce the levels of gamma amino-n-butyric acid (GABA) in the cortex. This effect of IBO on the inhibitory GABAergic system may contribute to the direct toxic effects of IBO which is mediated through excitatory amino acid receptors. Phencyclidine had no effect on the changes in GABA produced by IBO. The effect of phencyclidine treatment on IBO behavioural toxicity observed in this study demonstrates that antagonism of the phencyclidine receptor site on the N-methyl-D-aspartate receptor complex may be partially protective against the excitotoxic damage induced by IBO.
O'Connell
A
A
Pharmacology Department, University College, Galway, Ireland.
Earley
B
B
Leonard
B E
BE
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D007051:Ibotenic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007051:Ibotenic Acid; D005680:gamma-Aminobutyric Acid; D010622:Phencyclidine