Skip to main content
Journal cover image

The α₂-adrenergic antagonist idazoxan counteracts prepulse inhibition deficits caused by amphetamine or dizocilpine in rats.

Publication ,  Journal Article
Larrauri, JA; Levin, ED
Published in: Psychopharmacology (Berl)
January 2012

RATIONALE: Prepulse inhibition (PPI) is the reduction in startle response magnitude when intense stimuli are closely preceded by other weak stimuli. Animal models used to investigate sensorimotor gating deficits include both the stimulation of dopamine receptors (e.g., amphetamine or apomorphine) and the blockade of NMDA-glutamate receptors (e.g., dizocilpine or phencyclidine). OBJECTIVES: We assessed the effects of idazoxan (an α(2)-adrenergic antagonist) on amphetamine- and dizocilpine-induced PPI disruptions in adult female Sprague-Dawley rats. METHODS: In experiment 1, rats were tested for PPI in a bimodal paradigm with an acoustic prepulse and a tactile startle stimulus. Interactions of amphetamine (1 mg/kg) and idazoxan (0.5, 1, and 2 mg/kg) were assessed, with all rats receiving all drug doses in a counterbalanced order. In experiment 2, dizocilpine (0.05 mg/kg) and idazoxan (0.5, 1, and 2 mg/kg) interactions were analyzed. RESULTS: Amphetamine (1 mg/kg) caused a significant reduction in PPI. Both the 1- and 2-mg/kg doses of idazoxan significantly counteracted this effect. Dizocilpine (.05 mg/kg) effectively inhibited PPI, and the 2-mg/kg idazoxan dose significantly counteracted this impairment. CONCLUSIONS: These results suggest that the effectiveness of atypical antipsychotics such as clozapine in counteracting sensorimotor gating deficits reported in previous studies (e.g., Swerdlow and Geyer, Pharmacol Biochem Behav 44:741-744, 1993; Bakshi et al., J Pharmacol Exp Ther 271:787-794, 1994) may be related to their α(2)-antagonist effects, which may be a critical mechanism of the therapeutic effects of atypical antipsychotics in schizophrenia.

Duke Scholars

Published In

Psychopharmacology (Berl)

DOI

EISSN

1432-2072

Publication Date

January 2012

Volume

219

Issue

1

Start / End Page

99 / 108

Location

Germany

Related Subject Headings

  • Reflex, Startle
  • Receptors, Adrenergic, alpha-2
  • Rats, Sprague-Dawley
  • Rats
  • Psychiatry
  • Idazoxan
  • Female
  • Drug Interactions
  • Dose-Response Relationship, Drug
  • Dizocilpine Maleate
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Larrauri, J. A., & Levin, E. D. (2012). The α₂-adrenergic antagonist idazoxan counteracts prepulse inhibition deficits caused by amphetamine or dizocilpine in rats. Psychopharmacology (Berl), 219(1), 99–108. https://doi.org/10.1007/s00213-011-2377-2
Larrauri, José A., and Edward D. Levin. “The α₂-adrenergic antagonist idazoxan counteracts prepulse inhibition deficits caused by amphetamine or dizocilpine in rats.Psychopharmacology (Berl) 219, no. 1 (January 2012): 99–108. https://doi.org/10.1007/s00213-011-2377-2.
Larrauri, José A., and Edward D. Levin. “The α₂-adrenergic antagonist idazoxan counteracts prepulse inhibition deficits caused by amphetamine or dizocilpine in rats.Psychopharmacology (Berl), vol. 219, no. 1, Jan. 2012, pp. 99–108. Pubmed, doi:10.1007/s00213-011-2377-2.
Journal cover image

Published In

Psychopharmacology (Berl)

DOI

EISSN

1432-2072

Publication Date

January 2012

Volume

219

Issue

1

Start / End Page

99 / 108

Location

Germany

Related Subject Headings

  • Reflex, Startle
  • Receptors, Adrenergic, alpha-2
  • Rats, Sprague-Dawley
  • Rats
  • Psychiatry
  • Idazoxan
  • Female
  • Drug Interactions
  • Dose-Response Relationship, Drug
  • Dizocilpine Maleate