Long-term diazepam treatment produces changes in cholecystokinin receptor binding in rat brain.
This study examined the effect of chronic diazepam administration on central benzodiazepine and CCK-8 receptor binding in rat brain. After a two-week treatment with diazepam (5 mg/kg per day) tolerance developed towards the sedative but not towards the anxiolytic action of this drug as determined using elevated plus-maze and open field tests. The % entries the rats made onto open arms and % time the rats spent in open arms were markedly decreased 24 h after the last dose of diazepam, probably indicating withdrawal anxiety. There were no changes in [3H]flunitrazepam binding either 30 min or 24 h after the last diazepam dose. However, 30 min after the last diazepam administration the apparent number of sulphated [3H]CCK-8 binding sites was significantly increased in the primary olfactory cortex. Acute diazepam treatment (5 mg/kg) had no influence on [3H]flunitrazepam or sulphated [3H]CCK-8 binding in any brain region studied. Cessation of chronic diazepam treatment was followed after 24 h by an increase in the number of CCK-8 receptors in frontal cortex and hippocampus as compared to the vehicle group. These results demonstrate that certain alterations in CCK-8 receptor characteristics may be important in the anti-anxiety effect, tolerance, and withdrawal reaction reaction after benzodiazepine administration.
Harro
J
J
Psychopharmacology Laboratory, Tartu University, Estonia, U.S.S.R.
Lang
A
A
Vasar
E
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002766:Cholecystokinin / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D005445:Flunitrazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D011949:Receptors, Cholecystokinin; D005445:Flunitrazepam; D002766:Cholecystokinin; D003975:Diazepam