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>

Tournier, Benjamin; Ginovart, Nathalie

doi:10.1016/j.euroneuro.2014.04.003

Scientific article

English

Repeated but not acute treatment with ∆⁹-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D_{2/3lt;/sub> receptor antagonist haloperidol}

Contributors

Tournier, Benjamin; Ginovart, Nathalie

Published in

European neuropsychopharmacology, vol. 24, no. 8, p. 1415-1423

Publication date

2014

Abstract

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.

Keywords

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

UNIGE affiliation entities

Faculté de médecine / Section de médecine clinique / Département de psychiatrie

UNIGE research groups

Funding

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 ∆⁹-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D_{2/3lt;/sub> receptor antagonist haloperidol}. In: European neuropsychopharmacology, 2014, vol. 24, n° 8, p. 1415–1423. doi: 10.1016/j.euroneuro.2014.04.003

Article (Published version)

Identifiers

PID : unige:92575
DOI : 10.1016/j.euroneuro.2014.04.003
PMID : 24846537

Journal ISSN

0924-977X

570views

2downloads

Creation

15/03/2017 09:15:00

First validation

15/03/2017 09:15:00

Update

15/03/2023 01:27:57

Status update

15/03/2023 01:27:57

Last indexation

31/10/2024 06:26:53

Repeated but not acute treatment with ∆⁹-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D_{2/3lt;/sub> receptor antagonist haloperidol}

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

UNIGE research groups

Funding

Citation (ISO format)

Main files (1)

Identifiers

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation

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

Contributors

Published in

Publication date

Abstract

Keywords

UNIGE affiliation entities

UNIGE research groups

Funding

Citation (ISO format)

Main files (1)

Identifiers

Journal ISSN

Technical informations

Creation

First validation

Update

Status update

Last indexation

Repeated but not acute treatment with ∆⁹-tetrahydrocannabinol disrupts prepulse inhibition of the acoustic startle: reversal by the dopamine D_{2/3lt;/sub> receptor antagonist haloperidol}