Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP)

Patrick Michael Callahan, Kathryn A. Cunningham

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Rats were trained to discriminate the 5-HT receptor agonists m-chlorophenylpiperazine (mCPP; 1 mg/kg) from saline using a two-lever, water-reinforced drug discrimination task. The antidepressant trazodone (1-8 mg/kg), the 5-HT1B/2C receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP; 0.25-1 mg/kg) and MK 212 (0.125-1 mg/kg), and the mixed 5-HT1A/B receptor agonist RU 24969 (0.25-2 mg/kg) substituted fully for mCPP. The 5-HT2A/2C receptor agonists 1-(2,5-dimethoxy-4-iodophenyl) -2-aminopropane (DOI; 0.25-1 mg/kg) and d-lysergic acid diethylamide (LSD; 0.02-0.08 mg/kg) and the 5-HT releaser fenfluramine (0.5-2 mg/kg) also mimicked mCPP. Agonists selective for the 5-HT1A or 5-HT3 receptor or the 5-HT reuptake site produced saline-lever responding. The ergoline derivative mesulergine (0.5-4 mg/kg) produced a partial agonist/antagonist profile. The 5-HT 1 2 receptor antagonist metergoline (0.125-2 mg/kg) completely blocked the mCPP cue whereas the 5-HT2A/2C receptor antagonists ketanserin and LY 53857 as well as all other 5-HT receptor antagonists failed to block the mCPP cue. The dopamine receptor antagonists SCH 23390 and haloperidol were also ineffective mCPP antagonists. Following pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA; 100 mg/kg/day) for 3 consecutive days, the discriminability of low doses of mCPP increased, whereas the effects of fenfluramine decreased. The present results suggest that the discriminative stimulus effects of mCPP in rats are mediated primarily by postsynaptic 5-HT2C receptors.

Original languageEnglish (US)
Pages (from-to)27-38
Number of pages12
JournalEuropean Journal of Pharmacology
Volume257
Issue number1-2
DOIs
StatePublished - May 12 1994
Externally publishedYes

Fingerprint

Receptor, Serotonin, 5-HT2C
Fenfluramine
Receptor, Serotonin, 5-HT2A
Lysergic Acid Diethylamide
Serotonin
Serotonin Receptors
Cues
LY 53857
Ergolines
Metergoline
Serotonin 5-HT2 Receptors
Trazodone
Receptor, Serotonin, 5-HT1B
Fenclonine
Serotonin 5-HT1 Receptor Agonists
1-(3-chlorophenyl)piperazine
Receptors, Serotonin, 5-HT3
Serotonin Receptor Agonists
Ketanserin
Serotonin Antagonists

Keywords

  • (Rat)
  • 5-HT (5-hydroxytryptamine, serotonin)
  • 5-HT receptor
  • 5-HT receptor
  • 5-HT receptor
  • 5-HT receptor agonist
  • 5-HT receptor antagonist
  • Drug discrimination
  • mCPP (m-chlorophenylpiperazine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). / Callahan, Patrick Michael; Cunningham, Kathryn A.

In: European Journal of Pharmacology, Vol. 257, No. 1-2, 12.05.1994, p. 27-38.

Research output: Contribution to journalArticle

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