Detailed investigations of 5-HT3 compounds in a drug discrimination model

Richard De La Garza, Patrick Michael Callahan, Kathryn A. Cunningham

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Serotonin type-3 (5-HT3) receptors modulate both dopamine (DA) release and locomotor stimulation induced by cocaine, yet appear to be ineffective at blocking its stimulus and reinforcing effects. To more thoroughly characterize a potential modulatory role of 5-HT3 receptors in the stimulus effects of cocaine, rats (n = 8/group) were trained to discriminate cocaine (10 mg/kg, IP) or the 5-HT3 agonist 1-(meta-chlorophenyl)-biguanide (mCPBG: 15 mg/kg, IP) from saline using a standard drug discrimination task. In rats trained to discriminate cocaine, mCPBG (2.5-20 mg/kg) produced, at best, a partial substitution while mCPBG (10 mg/kg) did not alter the cocaine dose- response relationship. The 5-HT3 antagonists MDL 72222 (10 mg/kg) and ondansetron (1.25-16 mg/kg) did not attenuate the cocaine cue. In rats trained to discriminate mCPBG from saline, the 5-HT precursor l-5- hydroxytryptophan (12.5-50 mg/kg) dose-dependently substituted for mCPBG, whereas the 5-HT3 antagonist zacopride (0.1-10 mg/kg) partially antagonized the mCPBG cue, demonstrating that mCPBG produces distinct discriminable effects that appear to be mediated by 5-HT, possibly 5-HT3, receptors. However, cocaine (5-20 mg/kg) did not substitute in mCPBG-trained rats. Overall, these data support previous findings to suggest that 5-HT3 receptors play little role in mediating the discriminative stimulus effects of cocaine and suggest that the neurochemical mechanisms and/or sites of action important for the generation of the discriminative stimulus vs. locomotor stimulatory effects of cocaine may he dissociable.

Original languageEnglish (US)
Pages (from-to)533-540
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume54
Issue number3
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

Cocaine
Receptors, Serotonin, 5-HT3
Pharmaceutical Preparations
Rats
Serotonin 5-HT3 Receptor Antagonists
Serotonin
Cues
Serotonin 5-HT3 Receptor Agonists
Biguanides
Discrimination (Psychology)
Ondansetron
5-Hydroxytryptophan
1-(3-chlorophenyl)biguanide
Dopamine
Substitution reactions

Keywords

  • 5-HT receptors
  • Cocaine
  • Drug discrimination
  • MDL 72222
  • Ondansetron
  • Zacopride
  • mCPBG

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Cite this

Detailed investigations of 5-HT3 compounds in a drug discrimination model. / De La Garza, Richard; Callahan, Patrick Michael; Cunningham, Kathryn A.

In: Pharmacology Biochemistry and Behavior, Vol. 54, No. 3, 01.01.1996, p. 533-540.

Research output: Contribution to journalArticle

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