Enhanced benzodiazepine responsiveness in rats with increased cholinergic function.
The effects of diazepam and muscimol on locomotor activity were examined in Flinders Sensitive Line (FSL) rats, derived by selective breeding methods from randomly bred Sprague-Dawley (RB) rats for increased behavioural and physiological sensitivity to the anticholinesterase, diisopropylfluorophosphate (DFP). Previous reports of increased behavioural sensitivity to oxotremorine, associated with increased striatal and hippocampal muscarinic receptor concentrations, were confirmed in FSL rats compared to RB rats. The FSL rats were more sensitive to the locomotor suppressant effects of diazepam and muscimol compared to RB. Binding experiments with [3H]-diazepam showed that FSL rats had an increased benzodiazepine receptor concentration in the striatum and hippocampus compared to Flinders Resistant Line rats (FRL). FRL did not differ significantly from RB in diazepam-induced changes in locomotor activity or the concentration of benzodiazepine receptors. No significant differences in the affinity of benzodiazepine receptors was detected between the three rat lines in the brain regions investigated. Thus FSL rats showed an increased behavioural sensitivity to both diazepam and muscimol which was associated with a greater concentration of benzodiazepine receptors in the striatum and hippocampus compared to RB and FRL rats.
Pepe
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Department of Clinical Pharmacology, School of Medicine, Flinders University of South Australia.
Overstreet
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DH
Crocker
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D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains / Q000235:genetics; D011963:Receptors, GABA-A / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000187:drug effects / Q000235:genetics
D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D001569:Benzodiazepines; D009118:Muscimol; D010095:Oxotremorine; D003975:Diazepam