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

• Published in: Psychopharmacologia Vol. 166; no. 3; pp. 276 - 283
• Main Authors: LIANG, Jian-Hui, WANG, Xu-Hua, LIU, Rui-Ke, SUN, Hong-Lei, YE, Xiang-Feng, ZHENG, Ji-Wang
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.03.2003; Springer Nature B.V
• Subjects: 5-Hydroxytryptophan - pharmacology; Analgesics; Animals; Biological and medical sciences; Buspirone - pharmacology; Caffeine; Caffeine - pharmacology; Calcium - pharmacology; Calcium Channel Blockers - pharmacology; Calcium Channels, L-Type - drug effects; Calcium Chloride - pharmacology; Central Nervous System Stimulants - pharmacology; Chelating Agents - pharmacology; Egtazic Acid - pharmacology; Endorphins; Female; Fluoxetine - pharmacology; Injections, Intraventricular; Kinases; Medical sciences; Mice; Morphine; Narcotics; Neuropharmacology; Nifedipine - pharmacology; Pain Measurement - drug effects; Pharmacology. Drug treatments; Proteins; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Reaction Time - drug effects; Receptors, Serotonin - drug effects; Receptors, Serotonin, 5-HT1; Ryanodine - pharmacology; Serotonin Receptor Agonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Nociception; Partial agonist; Ryanodine; Intraperitoneal administration; Calcium; Fluoxetine; Psychotropic; Calcium channel blocker; The hot-plate test; Rodentia; Ionic channel; Biological activity; Dose activity relation; Vertebrata; Mammalia; Pain; 5-HT1A Serotonine receptor; Tranquillizer; Mouse; Animal; Buspirone; Mechanism of action; Voltage mode
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-002-1327-4

Previous studies have shown that buspirone, a partial 5-HT(1A) receptor agonist, produces antinociceptive effects in rats and mice; Ca(2+) plays a critical role as a second messenger in mediating nociceptive transmission. 5-HT(1A) receptors have been proven to be coupled functionally with various types of Ca(2+) channels in neurons, including N-, P/Q-, T-, or L-type. It was of interest to investigate the involvement of extracellular/intracellular Ca(2+) in buspirone-induced antinociception. To determine whether central serotonergic pathways participate in the antinociceptive processes of buspirone, and investigate the involvement of Ca(2+) mechanisms, particularly L-voltage-gated Ca(2+) channels and Ca(2+)/caffeine-sensitive pools, in buspirone-induced antinociception. Antinociception was assessed using the hot-plate test (55 degrees 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.), CaCl(2) (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.). 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 Ca(2+) reversed the antinociceptive effects of buspirone. In contrast to these, ryanodine or EGTA administered centrally potentiated buspirone-induced antinociception. Decreasing neuronal Ca(2+) levels potentiated buspirone-induced antinociception; conversely, increasing intracellular Ca(2+) abolished the antinociceptive effects of buspirone. These results suggest that Ca(2+) influx from extracellular fluid and release of Ca(2+) from Ca(2+)/caffeine-sensitive microsomal pools may be involved in buspirone-induced antinociception.