Scientific article

Repeated but not acute treatment with ∆9-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D2/3lt;/sub> receptor antagonist haloperidol

Published inEuropean neuropsychopharmacology, vol. 24, no. 8, p. 1415-1423
Publication date2014

Cannabis produces cognitive dysfunctions that resemble those of schizophrenia; yet the neurobiological substrate of this similarity remains unclear. Schizophrenia patients show deficits in prepulse inhibition (PPI) of the acoustic startle reflex (ASR), an operational measure of the information-processing abnormalities that may underlie the cognitive and positive symptoms of the disease. However, the effect of cannabis on PPI remains poorly understood, as data are often contradictory. Here, we investigated the effect of acute and repeated treatment with ∆(9)-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on PPI in rats, and the role of dopamine D₂/₃-receptor blockade in this effect. PPI and ASR were sequentially measured after the first and the last dose of a 21-days treatment with THC (1 mg/kg/day) or vehicle and at 1-week following discontinuation of treatment. The effect of haloperidol (0.1 mg/kg) on THC-induced PPI alteration was also evaluated. Chronic, but not acute, THC treatment produced significant reductions in PPI that were normalized back to control values within one-week of THC discontinuation. The THC-induced gating deficits were observed in the absence of ASR change and were reversed by the D₂/₃-receptor antagonist haloperidol. Chronic THC exposure induced PPI disruptions that emerged only following repeated administrations, suggesting that time-dependent neuroadaptations within the DA mesolimbic system are involved in the disruptive effects of THC on sensorimotor gating. These gating deficits were transient and appeared to be dependent on an overactivity of D₂/₃-receptor-mediated dopamine signaling, highlighting a potential role for D₂/₃-receptors in the propsychotic action of THC.

  • Acoustic Stimulation
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Dopamine Antagonists/therapeutic use
  • Dronabinol/toxicity
  • Gait Disorders, Neurologic/chemically induced/drug therapy
  • Hallucinogens/toxicity
  • Haloperidol/therapeutic use
  • Male
  • Prepulse Inhibition/drug effects
  • Psychoacoustics
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Swiss National Science Foundation - Effects of a subchronic treatment with Delta9-tetrahydrocannabinol (THC) on behavior and in vivo dopamine function: a positron emission tomography study in rats
Citation (ISO format)
TOURNIER, Benjamin, GINOVART, Nathalie. Repeated but not acute treatment with ∆<sup>9</sup>-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D<sub>2/3lt;/sub&gt; receptor antagonist haloperidol</sub>. In: European neuropsychopharmacology, 2014, vol. 24, n° 8, p. 1415–1423. doi: 10.1016/j.euroneuro.2014.04.003
Main files (1)
Article (Published version)
ISSN of the journal0924-977X

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