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RU 24969, a 5-HT1A/1B agonist, elevates brain stimulation reward thresholds: an effect reversed by GR 127935, a 5-HT1B/1D antagonist

Academic Article
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Overview

authors

  • Harrison, A. A.
  • Parsons, Loren (Larry)
  • Koob, George
  • Markou, A.

publication date

  • January 1999

journal

  • Psychopharmacology  Journal

abstract

  • Recent studies suggest that serotonergic neurotransmission through the serotonin-1B (5-HT1B) receptor is involved in reward processes. The purpose of the present studies was to investigate the effects of 5-HT(1B) receptor activation and antagonism on intracranial self-stimulation (ICSS) reward using a current-threshold ICSS task. Male Wistar rats were prepared with bipolar electrodes in the lateral hypothalamus. When stable baseline thresholds were established, the effects of the mixed 5-HT(1A)/1B receptor agonist, RU 24969 (0-1 mg/kg, SC), on ICSS behavior were assessed. Administration of this compound elevated ICSS thresholds without affecting response latencies, a measure of general motoric activity. The 5-HT(1B/1D) receptor antagonist, GR 127935 (0-10 mg/kg, SC), had no significant effect on ICSS behavior. However, pretreatment with an intermediate dose of GR 127935 (3 mg/kg), which was previously without effect on ICSS behavior, reversed the threshold-elevating effects of RU 24969 (1 mg/kg), suggesting the involvement of the 5-HT1B receptor in this effect of RU 24969 administration. Furthermore, pretreatment with RU 24969 (0.3 and 0.6 mg/kg), prior to 10 mg/kg cocaine hydrochloride, dose-dependently attenuated the threshold-reducing effects of cocaine. This result is interpreted as two opposing drug effects canceling each other out rather than a specific pharmacological antagonism. In conclusion, the results suggest that activation of 5-HT(1B) receptors reduces brain stimulation reward.

subject areas

  • Animals
  • Brain
  • Cocaine
  • Conditioning, Operant
  • Dopamine Uptake Inhibitors
  • Dose-Response Relationship, Drug
  • Electric Stimulation
  • Indoles
  • Male
  • Oxadiazoles
  • Piperazines
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Reward
  • Self Stimulation
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
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Research

keywords

  • 5-HT1B
  • GR 127935
  • RU 24969
  • cocaine
  • intracranial self-stimulation
  • reward
  • serotonin
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Identity

International Standard Serial Number (ISSN)

  • 0033-3158

Digital Object Identifier (DOI)

  • 10.1007/s002130050831

PubMed ID

  • 10027505
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Additional Document Info

start page

  • 242

end page

  • 250

volume

  • 141

issue

  • 3

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