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Buspirone-induced antinociception is mediated by l-type calcium channels and calcium/caffeine-sensitive pools in mice

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Abstract

Rationale

Previous studies have shown that buspirone, a partial 5-HT1A receptor agonist, produces antinociceptive effects in rats and mice; Ca2+ plays a critical role as a second messenger in mediating nociceptive transmission. 5-HT1A receptors have been proven to be coupled functionally with various types of Ca2+ channels in neurons, including N-, P/Q-, T-, or L-type. It was of interest to investigate the involvement of extracellular/intracellular Ca2+ in buspirone-induced antinociception.

Objectives

To determine whether central serotonergic pathways participate in the antinociceptive processes of buspirone, and investigate the involvement of Ca2+ mechanisms, particularly L-voltage-gated Ca2+ channels and Ca2+/caffeine-sensitive pools, in buspirone-induced antinociception.

Methods

Antinociception was assessed using the hot-plate test (55°C, hind-paw licking latency) in mice treated with either buspirone (1.25–20 mg/kg i.p.) alone or the combination of buspirone and fluoxetine (2.5–10 mg/kg i.p.), 5-HTP (25 mg/kg i.p.), nimodipine (2.5–10 mg/kg i.p.), nifedipine (2.5–10 mg/kg i.p.), CaCl2 (25–200 nmol per mouse i.c.v.), EGTA (5–30 nmol per mouse i.c.v.), or ryanodine (0.25–2 nmol per mouse i.c.v.).

Results

Buspirone dose dependently increased the licking latency in the hot-plate test in mice. This effect of buspirone was enhanced by fluoxetine, 5-HTP, nimodipine, and nifedipine. Interestingly, central administration of Ca2+ reversed the antinociceptive effects of buspirone. In contrast to these, ryanodine or EGTA administered centrally potentiated buspirone-induced antinociception.

Conclusions

Decreasing neuronal Ca2+ levels potentiated buspirone-induced antinociception; conversely, increasing intracellular Ca2+ abolished the antinociceptive effects of buspirone. These results suggest that Ca2+ influx from extracellular fluid and release of Ca2+ from Ca2+/caffeine-sensitive microsomal pools may be involved in buspirone-induced antinociception.

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Acknowledgements

We thank Dr. Mogens Nielsen (Royal School of Pharmacy, Universitetsparken 2, Denmark) and Dr. Hanting Zhang (University of Tennessee Health Science Center, USA) for their advice and assistance.

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  1. Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, 100083, Beijing , P.R. China

    Jian-Hui Liang, Xu-Hua Wang, Rui-Ke Liu, Hong-Lei Sun, Xiang-Feng Ye & Ji-Wang Zheng

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  1. Jian-Hui Liang
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Liang, JH., Wang, XH., Liu, RK. et al. Buspirone-induced antinociception is mediated by l-type calcium channels and calcium/caffeine-sensitive pools in mice. Psychopharmacology 166, 276–283 (2003). https://doi.org/10.1007/s00213-002-1327-4

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