PMID: 8968382Dec 1, 1996Paper

Chronic antidepressant exposure enhances 5-hydroxytryptamine7 receptor-mediated cyclic adenosine monophosphate accumulation in rat frontocortical astrocytes

The Journal of Pharmacology and Experimental Therapeutics
M ShimizuS Yamawaki

Abstract

In rat frontal cortical astrocytes, 5-hydroxytryptamine (5-HT), 5-carboxamidotryptamine and 5-methoxytryptamine elicited a concentration-dependent increase of cyclic AMP accumulation, with EC50 values of 137 +/- 7 nM (5-HT), 10.4 +/- 3.9 nM (5-carboxamidotryptamine) and 57.8 +/- 13.6 nM (5-methoxytryptamine). Accumulation of cyclic AMP stimulated by 5-HT (10 microM) was inhibited by methiothepin (IC50 = 21 +/- 13 nM) but not by pindolol, SCH 23390, ICS 205-930 or GR 113808. These pharmacological effects on cyclic AMP formation in astrocytes are consistent with those observed in 5-HT7 receptor binding studies. Indeed, reverse transcription-polymerase chain reaction analysis revealed the presence of 5-HT7 mRNA in astrocytes. Chronic exposure of astrocytes to mianserin (0.05-4 microM) or amitriptyline (1-8 microM) for 3 days produced a concentration-dependent enhancement of 5-HT-stimulated cyclic AMP accumulation, with EC50 values of 0.47 +/- 0.04 microM (mianserin) and 2.5 +/- 0.3 microM (amitriptyline). The enhancement of cyclic AMP accumulation was time dependent, reaching maximal levels within 2 days. Mianserin exposure (2 microM, for 3 days) resulted in a comparable enhancement of cyclic AMP accumulation mediated by 5-carboxa...Continue Reading

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