Discriminative stimulus effects of 5.6 mg/kg pregnanolone in DBA/2J and C57BL/6J inbred mice

Erin E. Shannon, Robert H. Purdy, Kathleen (Kathy) Grant

Research output: Contribution to journalArticle

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Abstract

Neurosteroids represent a class of endogenous compounds that exert rapid, nongenomic effects through neurotransmitter receptor systems such as γ-aminobutyric acidA (GABAA). Two neurosteroids, allopregnanolone (3α-hydroxy-5α-pregnan-20-one) and pregnanolone (3α-hydroxy-5β-pregnan-20-one), possess anxiolytic and sedative properties and show substitution for ethanol, benzodiazepines, and barbiturates in drug discrimination assays. A previous study examining the discriminative stimulus effects of 10 mg/kg pregnanolone in DBA/2J and C57BL/6J mice showed pregnanolone's discriminative stimulus to be mediated primarily through GABAA positive modulation. This study examined the discriminative stimulus effects of a lower training dose (5.6 mg/kg) of pregnanolone in DBA/2J and C57BL/5J mice. Twelve male DBA/2J mice and 12 male C57BL/6J mice were trained to discriminate 5.6 mg/kg pregnanolone. GABAA-receptor positive modulators, neuroactive steroids, NMDA receptor antagonists, and 5-HT3 receptor agonists were tested for pregnanolone substitution. In DBA/2J and C57BL/6J mice benzodiazepine, barbiturate, and GABAergic neuroactive steroids all substituted for pregnanolone. In the DBA/2J mice, NMDA receptor antagonists showed generalization to the discriminative stimulus cues of pregnanolone, an effect not seen in the C57BL/6J mice. 5-HT3 receptor agonists and zolpidem failed to substitute for pregnanolone's discriminative stimulus in either strain. AlloTHDOC and midazolam were more potent in producing pregnanolone-like discriminative stimulus effects in DBA/2J mice. These results provide a comprehensive look at pregnanolone's discriminative stimulus effects in two commonly used strains of mice. The present data suggest GABA A-receptor positive modulation as the predominant receptor mechanism mediating the discriminative stimulus effects of pregnanolone. NMDA receptor antagonism was suggested in the DBA/2J mice and may represent a heterogenous cue produced by the lower training dose of pregnanolone.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalAlcohol
Volume37
Issue number1
DOIs
StatePublished - Aug 2006
Externally publishedYes

Fingerprint

Pregnanolone
Inbred C57BL Mouse
stimulus
Inbred DBA Mouse
substitution
Serotonin 5-HT3 Receptor Agonists
N-Methyl-D-Aspartate Receptors
Receptors, Serotonin, 5-HT3
GABA-A Receptors
antagonism
Benzodiazepines
Cues
Neurotransmitter Agents
Substitution reactions
Modulation
discrimination
Barbiturates
Neurotransmitter Receptor
drug
Steroid Receptors

Keywords

  • C57BL/6J
  • DBA/2J
  • Drug discrimination
  • Neurosteroid
  • Pregnanolone

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neuroscience(all)
  • Toxicology
  • Health(social science)

Cite this

Discriminative stimulus effects of 5.6 mg/kg pregnanolone in DBA/2J and C57BL/6J inbred mice. / Shannon, Erin E.; Purdy, Robert H.; Grant, Kathleen (Kathy).

In: Alcohol, Vol. 37, No. 1, 08.2006, p. 35-45.

Research output: Contribution to journalArticle

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