Possible involvement of CA1 5-HT1B/1D and 5-HT2A/2B/2C receptors in harmaline-induced amnesia

Pharmacol Biochem Behav. 2014 Oct:125:70-77. doi: 10.1016/j.pbb.2014.08.007. Epub 2014 Aug 30.

Abstract

In the present study, effects of the serotonergic system of the dorsal hippocampus (CA1) on harmaline-induced amnesia were examined. A single-trial step-down passive avoidance task was used for the assessment of memory retention in adult male NMRI mice. Pre-training intra-peritoneal (i.p.) administration of harmaline (1mg/kg) induced impairment of memory retention. Moreover, intra-CA1 administration of 5-HT1B/1D receptor agonist, CP94253 (5 ng/mouse), 5-HT1B/1D receptor antagonist, GR127935 (0.05 and 0.5 ng/mouse), 5-HT2A/2B/2C receptor agonist, α-methyl 5-HT (0.5 ng/mouse) and 5-HT2 receptor antagonist, cinancerine (0.5 ng/mouse) impaired memory acquisition, but did not affect locomotor activity and tail flick. Furthermore, pre-training intra-CA1 injection of subthreshold dose of CP94253 (0.05 ng/mouse) or GR127935 (0.005 ng/mouse) reversed impairment of memory acquisition induced by harmaline (1 mg/kg, i.p.). However, pre-training intra-CA1 infusion of subthreshold dose of α-methyl 5-HT (0.005 ng/mouse) or cinancerine (0.005 ng/mouse) with the administration of harmaline (0.5 and 1 mg/kg, i.p.) heighten impairment of memory acquisition. These findings implicate the involvement of CA1 serotonergic mechanism in harmaline-induced impairment of memory acquisition.

Keywords: Harmaline; Memory; Mice; Passive avoidance; Serotonergic system.

MeSH terms

  • Amnesia / chemically induced*
  • Animals
  • CA1 Region, Hippocampal / drug effects*
  • CA1 Region, Hippocampal / physiology
  • Central Nervous System Stimulants / pharmacology*
  • Cinanserin / pharmacology
  • Harmaline / pharmacology*
  • Male
  • Memory / drug effects
  • Mice, Inbred Strains
  • Oxadiazoles / pharmacology
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1B / drug effects*
  • Receptor, Serotonin, 5-HT1B / physiology
  • Receptor, Serotonin, 5-HT1D / drug effects*
  • Receptor, Serotonin, 5-HT1D / physiology
  • Receptor, Serotonin, 5-HT2A / drug effects*
  • Receptor, Serotonin, 5-HT2A / physiology
  • Receptor, Serotonin, 5-HT2B / drug effects*
  • Receptor, Serotonin, 5-HT2B / physiology
  • Receptor, Serotonin, 5-HT2C / drug effects*
  • Receptor, Serotonin, 5-HT2C / physiology
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Serotonin 5-HT1 Receptor Agonists / pharmacology
  • Serotonin 5-HT1 Receptor Antagonists / pharmacology

Substances

  • CP 94253
  • Central Nervous System Stimulants
  • Oxadiazoles
  • Piperazines
  • Pyridines
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT1D
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2B
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT1 Receptor Agonists
  • Serotonin 5-HT1 Receptor Antagonists
  • alpha-methylserotonin
  • GR 127935
  • Serotonin
  • Harmaline
  • Cinanserin