Chronic imipramine increases platelet non-cyanoimipramine (CNIMI) binding but decreases cnimi specific binding

treatments at all doses used. The increases m HVA levels m the S were blunted after repeated H injections at doses of 0.5-l m&kg, suggesting that H pretreatment results in a decreased responsiveness to the drug at high doses (tolerance). Tolerance also developed to the action of long-term H treatment on HVA elevations in the PC at the highest dose used ( 1 mg/kg), suggesting that the differences in tolerance development ~ between S and PC, are not absolute and qualitative but relative and quantitative. However, repeated H injections at doses of 0.01-0.05 mg/kg can enhance the increases in HVA levels, suggesting that tolerance does not develop after chronic H treatment at low dosages. Decreased HVA concentration after withdrawal from chronic H treatment was also found (rebound decrease). However. this rebound decrease was much smaller than the tolerant HVA responsiveness, suggesting different mechanisms between them. Our results do not support the megadose H treatment in clinical settings.

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CHRONIC IMIPRAMINE INCREASES PLATELET NON-CYANOIMIPRAMINE (CNIMI) BINDING BUT DECREASES CNIMI SPECIFIC BINDING Edward DeMet, Kate Bell, Robert Gerner, Christopher Reist, Aleksandra Chicz-DeMet Irvine, CA Two subclasses of 3H-IMI binding sites were distinguished using CNIMI inhibition. Sites specific for CNIMI are trypsin sensitive (proteinaceous), and Na-dependent, whereas non-CNIMI sites are not. Total 3H-IMI binding was better correlated with non-CNIMI than CNIMI binding although both correlations were significant. Both CNIMI and non-CNIMI binding were reduced in endogenous unipolar depressed patients relative to controls although only the former was significant. Chronic imipramine treatment (6 week) significantly increased total 3H-IMI binding. Even larger increases were found in non-CNIMI binding. In contrast, CNIMI specific binding was significantly reduced by imipramine treatment. Highly significant inverse correlations were found between post-treatment cortisol and total 3H-IMI binding and non-CNIMI specific binding, whereas post-treatment cortisol was not related to CNIMI binding. The results suggest that a CNIMI specific subclass of 3H-IMI binding sites may be a trait marker of depressive illness, whereas non-CNIMI binding may fluctuate with plasma cortisol levels.

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AN AUTORADIOGRAPHIC STUDY OF MIANSERIN-INDUCED DOWN REGULATION OF SEROTONIN (5HTz AND 5HTlc) RECEPTORS Bryan L. Roth, Linda Decker, Miles Herkenham Stanford,

CA and Bethesda,

MD

Serotonin (5hydroxytryptamine; 5HT) selective uptake blockers (fluoxetine, zimelidine) as well as 5HT receptor antagonists (mianserin) are clinically useful antidepressants. Chronic treatment with these antidepressants in rats has caused downregulation of cortical 5HT2 receptors. Questions remain regarding: (1) the anatomical loci of the down- regulated receptors as well as (2) whether other 5HT receptor subtypes are similarly altered. Accordingly, we injected Sprague-Dawley rats with mianserin (10 mg/kg ip X 3 days) and after sacrifice prepared brains for receptor autoradiography