The neuroprotective effect of tacrine on trimethyltin induced memory and muscarinic receptor dysfunction in the rat.
In this study chronic (39 days) tacrine (3 mg/kg i.p.) treatment significantly improved trimethyltin (8 mg/kg i.p.) induced deficits in spatial navigation. Tacrine also reduced trimethyltin induced hyperactivity and passive avoidance deficits but these effects did not reach statistical significance. The effect of trimethyltin on muscarinic (M1 and M2) receptor sites was determined by means of quantitative autoradiography using [3H]quinuclidinyl benzilate. A selective pattern of M1 and M2 receptor loss was observed mainly affecting the hippocampus and other limbic structures while leaving other brain regions intact. Tacrine successfully prevented the M1 and M2 receptor loss in the CA1 and CA4 hippocampal subfields. The improvement in trimethyltin behavioural toxicity following tacrine treatment may be related to the protective effect of this compound on muscarinic receptor density in the hippocampal formation and lends support to the hypothesis that cholinergic system dysfunction may be primarily responsible for trimethyltin induced deficits in cognitive function.
O'Connell
A
A
Pharmacology Department, University College, Galway, Ireland.
Earley
B
B
Leonard
B E
BE
D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000187:drug effects; D050487:Glycine Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013619:Tacrine / Q000494:pharmacology*; D014298:Trimethyltin Compounds
D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D050487:Glycine Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; D011976:Receptors, Muscarinic; D014298:Trimethyltin Compounds; C046488:trimethyltin; D013619:Tacrine