Paroxetine as a 5-HT
neuroendocrine probe
H. Kojima, T. Terao, M. Iwakawa, A. Soya, N. Inoue, Y.
Shiraishi, Y. Son, S. Soeda, N. Ueda, R. Yoshimura, J.
Nakamura
A1 Department of Psychiatry, University of
Occupational and Environmental Health School of Medicine,
Yahatanishi-ku, Kitakyushu 807--8555, Japan
Abstract:
Abstract
Rationale. Acute administration of 40 mg paroxetine (a
selective serotonin reuptake inhibitor) reportedly increases
plasma cortisol in human subjects. This suggests that
paroxetine may be a useful tool to probe brain serotonin
function.
Objective. To investigate a dose-response relationship for
paroxetine administration, and to determine whether a lower
dose of paroxetine is sufficient to increase plasma ACTH and
cortisol.
Methods. Twenty subjects were tested on three occasions in
a double-blind, cross-over design receiving: (a) placebo, (b)
paroxetine 20 mg and (c) paroxetine 40 mg administered orally
at 8.00 a.m. In addition, five of the 20 subjects received
paroxetine 20 mg plus cyproheptadine (a 5-HT2
receptor antagonist) 4 mg and four subjects were given
paroxetine 40 mg plus cyproheptadine 4 mg in an open manner.
Plasma ACTH and cortisol levels were measured prior to
administration and every hour for 6 h thereafter.
Results. Paroxetine, particularly 20 mg rather than 40 mg,
significantly increased plasma ACTH and cortisol. Paroxetine
40 mg but not 20 mg caused significantly more nausea than the
placebo. Cyproheptadine attenuated ACTH and cortisol responses
to 20 mg but not to 40 mg paroxetine.
Conclusions. Low-dose (20 mg) paroxetine has greater
potential utility than larger doses as a neuroendocrine
challenge test. The endocrine responses to paroxetine are
probably mediated at least partially by 5-HT2A/2C
receptors.
Keywords:
Paroxetine, ACTH, Cortisol, Serotonin, 5-HT 2A receptor,
5-HT 2C receptor
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