Chronic Barbital Treatment and Cholinergic Mechanisms in Brain
Forced long term treatment (30–40 weeks) with barbital to rats in their drinking fluid has proved to be a useful method for inducing changes in cholinergic mechanisms in the brain which are related to tolerance and physical dependence and which could be regarded as adaptive changes in the cholinergic system revealed during abstinence (18). When rats are receiving barbital in their drinking fluid (3.33 mg/ml) the daily intake of barbital is about 200 mg/kg (14). Animals drinking barbital in this manner are initially sedated but this sedation disappears as the treatment continues. In the experiments reported here the treatments usually lasted for more than 30 weeks. At the end of the treatment the barbital solution is replaced by water (day 0); the days in abstinence are then counted consecutively. Changes in tolerance in the brain can be followed during abstinence by a hexobarbital threshold and such a tolerance toward barbiturates has been measured up to day 60 in the abstinence (Wahlstrom and Nordberg, this volume). That cholinergic mechanisms could be involved in the sensitivity to barbiturates measured with the hexobarbital threshold was indicated by the finding that an acute injection of pilocarpine or physostigmine increased the hexobarbital threshold while atropine decreased it (15–17). This idea has been strongly supported by recent results which show that that effect of atropine is restricted to only one of the isomers of hexobarbital (10).
KeywordsSpecific Radioactivity Cholinergic Mechanism High Affinity Uptake Drinking Fluid Quinuclidinyl Benzilate
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