Effects of RO 60 0175, a 5-HT(2C) receptor agonist, in three animal models of anxiety

Eur J Pharmacol. 2000 Jan 10;387(2):197-204. doi: 10.1016/s0014-2999(99)00706-2.

Abstract

There is some controversy as to whether 5-HT(2C) receptor agonists are anxiogenic or anxiolytic. The effects of the novel 5-HT(2C) receptor agonist, (S)-2-chloro-5-fluoro-indol-1-yl)-1-methyl ethylamine fumarate (RO 60 0175), in three models of anxiety were therefore tested. RO 60 0175 was found to induce hypolocomotion in rats at doses greater than 0.5 mg/kg s.c., an effect reversed by the selective 5-HT(2C) receptor antagonist, SB-242084. RO 60 0175 did not elicit anxiolytic-like responses in the social interaction test under high light unfamiliar conditions, but suppressed both time spent in social interaction and locomotion at doses of 1 and 3 mg/kg s.c., suggesting a sedative response. In the Vogel conflict test, RO 60 0175 had no significant action on the number of shocks taken. In the Geller-Seifter test, RO 60 0175 (0.3 and 1 mg/kg s.c.) simultaneously reduced both unpunished and punished lever pressing, a profile consistent with sedation. Finally, RO 60 0175 was tested in a rat social interaction test under low light familiar conditions optimal for the detection of anxiogenic-like responses. At 1 and 3 mg/kg s.c., RO 60 0175 reduced both time spent in social interaction and concurrent locomotion, a profile more consistent with sedation than anxiogenesis. In conclusion, RO 60 0175 induced sedative-like responses via 5-HT(2C) receptor activation, but was neither anxiolytic, nor clearly anxiogenic at the doses tested.

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / drug therapy
  • Behavior, Animal / drug effects
  • Ethylamines / pharmacology*
  • Hypnotics and Sedatives / pharmacology*
  • Indoles / pharmacology*
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / physiology*
  • Serotonin Receptor Agonists / pharmacology*
  • Social Behavior

Substances

  • Ethylamines
  • Hypnotics and Sedatives
  • Indoles
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Ro 60-0175
  • Serotonin Receptor Agonists