title: Differences between mice strains in response to paroxetine in the forced swimming test: involvement of serotonergic or noradrenergic systems.
abstract: We studied the effect of the selective serotonin reuptake inhibitor (SSRI) paroxetine on the immobility time in the forced swimming test using different strains of mice (ICR, ddY, C57BL/6, BALB/c and DBA/2). There was a difference between strains in the response to paroxetine (although it induced anti-immobility effects in all strains of mice used). The mouse strain most sensitive to paroxetine was DBA/2; the ICR strain showed the lowest sensitivity. We previously demonstrated variations in the responses to another SSRI, fluvoxamine, in different strains of mice, which was in agreement with the present findings. In DBA/2 and ICR mice, the anti-immobility effects of paroxetine were significantly antagonized by the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY 100635). The noradrenergic α(1)-adrenoceptor antagonist prazosin significantly reduced the anti-immobility effects elicited by a high dose (5mg/kg) of paroxetine in DBA/2 and ICR mice. However, prazosin did not affect the anti-immobility effects of a lower dose of paroxetine (1mg/kg) in DBA/2 mice. This suggests that the anti-immobility effects of a higher dose of paroxetine in mice are associated with serotonergic and noradrenergic neurons. Prazosin did not the affect anti-immobility effects of fluvoxamine. These results suggest that there are differences between mice strains in the antidepressant-like effects of paroxetine (which are similar to those elicited by fluvoxamine). Moreover, involvement of the noradrenergic system was partly related to the anti-immobility effects of paroxetine (which are different to those elicited by fluvoxamine).
authors: Laboratory of Pharmacology, Department of Clinical Pharmacy, Yokohama College of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama 245-0066, Japan. yumisugi@hamayaku.ac.jp
authors: Yumi
authors: Y
authors: Sugimoto
authors: Masami
authors: M
authors: Yamamoto
authors: Noriko
authors: N
authors: Tagawa
authors: Yoshiharu
authors: Y
authors: Kobayashi
authors: Kumiko
authors: K
authors: Mitsui-Saitoh
authors: Yoshihiro
authors: Y
authors: Hotta
authors: Jun
authors: J
authors: Yamada
mesh_terms: D059331:Adrenergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D016666:Fluvoxamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D017374:Paroxetine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism; D059326:Serotonergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D013045:Species Specificity; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017374:Paroxetine; D016666:Fluvoxamine; D011224:Prazosin