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

Richard De La Garza, Patrick M. Callahan, Kathryn 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 - Jul 1996

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
  • mCPBG
  • MDL 72222
  • Ondansetron
  • Zacopride

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

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

In: Pharmacology Biochemistry and Behavior, Vol. 54, No. 3, 07.1996, p. 533-540.

Research output: Contribution to journalArticle

De La Garza, Richard ; Callahan, Patrick M. ; Cunningham, Kathryn. / Detailed investigations of 5-HT3 compounds in a drug discrimination model. In: Pharmacology Biochemistry and Behavior. 1996 ; Vol. 54, No. 3. pp. 533-540.
@article{dedd503d380544d08550c16a4275b7cd,
title = "Detailed investigations of 5-HT3 compounds in a drug discrimination model",
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.",
keywords = "5-HT receptors, Cocaine, Drug discrimination, mCPBG, MDL 72222, Ondansetron, Zacopride",
author = "{De La Garza}, Richard and Callahan, {Patrick M.} and Kathryn Cunningham",
year = "1996",
month = "7",
doi = "10.1016/0091-3057(95)02207-4",
language = "English (US)",
volume = "54",
pages = "533--540",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Detailed investigations of 5-HT3 compounds in a drug discrimination model

AU - De La Garza, Richard

AU - Callahan, Patrick M.

AU - Cunningham, Kathryn

PY - 1996/7

Y1 - 1996/7

N2 - 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.

AB - 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.

KW - 5-HT receptors

KW - Cocaine

KW - Drug discrimination

KW - mCPBG

KW - MDL 72222

KW - Ondansetron

KW - Zacopride

UR - http://www.scopus.com/inward/record.url?scp=0029942974&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029942974&partnerID=8YFLogxK

U2 - 10.1016/0091-3057(95)02207-4

DO - 10.1016/0091-3057(95)02207-4

M3 - Article

C2 - 8743626

AN - SCOPUS:0029942974

VL - 54

SP - 533

EP - 540

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

IS - 3

ER -