title: Buspirone-induced antinociception is mediated by L-type calcium channels and calcium/caffeine-sensitive pools in mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.).
  
  
  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 Ca(2+) reversed the antinociceptive effects of buspirone. In contrast to these, ryanodine or EGTA administered centrally potentiated buspirone-induced antinociception.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, 38 Xueyuan Road, 100083, Beijing, P.R. China. liangjh@hotmail.com
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Liang
authors.forename: Xu-Hua
authors.initials: XH
authors.lastname: Wang
authors.forename: Rui-Ke
authors.initials: RK
authors.lastname: Liu
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Sun
authors.forename: Xiang-Feng
authors.initials: XF
authors.lastname: Ye
authors.forename: Ji-Wang
authors.initials: JW
authors.lastname: Zheng
mesh_terms: D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002122:Calcium Chloride / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D009543:Nifedipine / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012433:Ryanodine / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
chemical_list: D006916:5-Hydroxytryptophan; D000700:Analgesics; D002065:Buspirone; D002110:Caffeine; D002118:Calcium; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002122:Calcium Chloride; D000697:Central Nervous System Stimulants; D002614:Chelating Agents; D004533:Egtazic Acid; D005473:Fluoxetine; D009543:Nifedipine; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012433:Ryanodine; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors