Effects of amitriptyline on GABA-stimulated 36CI- uptake in relation to a behavioral model of depression.
The dominant-submissive relationship established between two rats competing for food is a model of depression and is used here to divide animals into two behaviorally distinct groups. Basal and GABA-stimulated 36CI- uptake was investigated for both dominant and submissive rats as well as the in vitro effect of the antidepressant amitriptyline (AMI). Because the antidepressant action of AMI only appears after chronic treatment, the effect of chronic injections of AMI on these behavioral and biochemical measures was also studied. Basal 36CI- uptake is significantly higher for dominant rats than for submissive rats. Increasing concentrations of AMI added to membrane vesicles enhanced 30 microM GABA-stimulated chloride uptake for dominant rats and inhibited it for submissive rats. Chronic treatment of dominant and submissive rats with AMI reversed these in vitro effects. The biochemical data correspond to the changes of the rats behavior in the dominance test after chronic treatment with AMI. However, this correlation is more clear for dominant than for submissive rats. Specific chloride influx was used as a measure of the sensitivity of GABAA receptor to GABA. This revealed different sensitivity states for GABAA receptors in tissues obtained from dominant and submissive rats. It is possible that the distinct conformational states of GABAA receptor are responsible for differences in rats behavior and in vitro effects of AMI before and after in vivo treatment of rats with this anti-depressant.
Malatynska
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University of Arizona, College of Medicine, Department of Pharmacology, Tucson 85724, USA.
De Leon
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I
Allen
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Yamamura
H I
HI
D000639:Amitriptyline / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002713:Chlorine / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D008297:Male; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011868:Radioisotopes; D000639:Amitriptyline; D002713:Chlorine; D005680:gamma-Aminobutyric Acid