Effects of chronic oral administration of the antidepressants, desmethylimipramine and zimelidine on rat cortical GABAB binding sites: a comparison with 5-HT2 binding site changes.
1. The effects of chronic oral administration of desmethylimipramine (DMI) or zimelidine (1.25 and 5 mg kg-1 twice daily for 21 days) were studied on rat whole cortical gamma-aminobutyric acidB (GABAB) binding sites. No changes in receptor affinity or number were found with either drug. 2. A subsequent study of GABAB binding sites using higher doses of these drugs (5 and 10 mg kg-1) and rat frontal cortex was also without effect, when investigated 24 h after termination of drug administration or 72 h after DMI administration (5 mg kg-1). 3. The number of frontal cortical 5-hydroxytryptamine2 (5-HT2) binding sites was significantly and dose-dependently decreased after both drugs, whereas the number of hippocampal 5-HT2 binding sites was not significantly altered after either drug. 4. As the number of frontal cortical GABAB binding sites was unaltered whereas the number of 5-HT2 binding sites was significantly decreased under identical study conditions, it may be concluded that the effects of antidepressant administration upon GABAB binding sites is a less consistent observation than their effects on 5-HT2 binding sites.
Cross
J A
JA
Department of Pharmacology & Clinical Pharmacology, St George's Hospital Medical School, London.
Horton
R W
RW
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology* / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D015031:Zimeldine / Q000494:pharmacology* / Q000633:toxicity
D000928:Antidepressive Agents; D011963:Receptors, GABA-A; D015031:Zimeldine; D007650:Ketanserin; D003891:Desipramine