N Salomé1, J Stemmelin, C Cohen, G Griebel. 1. Sanofi-Aventis, Department of Psychopharmacology, 31 avenue Paul Vaillant-Couturier, Bagneux 92220, France.
Abstract
RATIONALE: SSR149415 ((2S, 4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide), the first selective nonpeptide vasopressin V1b receptor antagonist has been shown to induce antidepressant-and anxiolytic-like effects following systemic administration, whereas intraseptal infusion of the drug engender antidepressant-but not anxiolytic-like effects. OBJECTIVES: Based on recent evidence that V1b receptors are located within the amygdaloid complex, a structure which is well known for its modulatory role of emotional processes, the possible involvement of the different amygdaloid nuclei in the anxiolytic- and/or antidepressant-like effects of SSR149415 was examined. METHODS: Male Sprague-Dawley or Wistar rats were infused with SSR149415 into the central (CeA), the basolateral (BlA), or the medial (MeA) nucleus of the amygdala and tested 10 min after microinjection in the elevated plus-maze or the forced-swimming test, two models typically used for assessing the anxiolytic and antidepressant effects of drugs, respectively. RESULTS: Microinjection of SSR149415 into the BlA (1-10 ng), but not into the CeA or the MeA, increased the percentage of time spent in the open arms of the elevated plus-maze, indicating anxiolytic-like effects. Furthermore, in the forced-swimming test, microinjection of the drug into the CeA (1, 10, and 100 ng), BlA (1-10 ng), or MeA (100 ng) decreased immobility, an effect which is indicative of an antidepressant-like action. Together, these findings indicate that while the antidepressant-like effects of SSR149415 are mediated by different amygdaloid nuclei, its anxiolytic-like effects appear to involve only the basolateral nucleus of the amygdala. Moreover, these results add further evidence to the role of extrahypothalamic vasopressinergic systems in the control of emotional responses.
RATIONALE: SSR149415 ((2S, 4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide), the first selective nonpeptide vasopressin V1b receptor antagonist has been shown to induce antidepressant-and anxiolytic-like effects following systemic administration, whereas intraseptal infusion of the drug engender antidepressant-but not anxiolytic-like effects. OBJECTIVES: Based on recent evidence that V1b receptors are located within the amygdaloid complex, a structure which is well known for its modulatory role of emotional processes, the possible involvement of the different amygdaloid nuclei in the anxiolytic- and/or antidepressant-like effects of SSR149415 was examined. METHODS: Male Sprague-Dawley or Wistar rats were infused with SSR149415 into the central (CeA), the basolateral (BlA), or the medial (MeA) nucleus of the amygdala and tested 10 min after microinjection in the elevated plus-maze or the forced-swimming test, two models typically used for assessing the anxiolytic and antidepressant effects of drugs, respectively. RESULTS: Microinjection of SSR149415 into the BlA (1-10 ng), but not into the CeA or the MeA, increased the percentage of time spent in the open arms of the elevated plus-maze, indicating anxiolytic-like effects. Furthermore, in the forced-swimming test, microinjection of the drug into the CeA (1, 10, and 100 ng), BlA (1-10 ng), or MeA (100 ng) decreased immobility, an effect which is indicative of an antidepressant-like action. Together, these findings indicate that while the antidepressant-like effects of SSR149415 are mediated by different amygdaloid nuclei, its anxiolytic-like effects appear to involve only the basolateral nucleus of the amygdala. Moreover, these results add further evidence to the role of extrahypothalamic vasopressinergic systems in the control of emotional responses.
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