Skip to content

Delta(9)-THC-induced cognitive deficits in mice are reversed by the GABA(A) antagonist bicuculline.

Stephen A Varvel, E Anum, F Niyuhire, Laura E Wise, Aron H Lichtman

Psychopharmacology March 2005 DOI: 10.1007/s00213-004-1988-2 (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Preclinical animal study Peer reviewed
Population Mice, including CB(1) receptor knockout and wild-type strains
Interventions Delta(9)-tetrahydrocannabinol (Delta(9)-THC) bicuculline CGP 36742 muscimol SR 141716
Dose 10 mg/kg Delta(9)-THC
Measures Morris water maze task, T-maze task
Topics Cannabis
Key points Bicuculline, a GABA(A) antagonist, completely reversed Delta(9)-THC-induced memory deficits in the Morris water maze and T-maze, whereas the GABA(B) antagonist CGP 36742 did not. CB(1) knockout mice were supersensitive to muscimol-induced water maze deficits, but SR 141716-treated wild-type mice responded to muscimol like vehicle-treated controls. The authors argue that GABA(A) receptors may be necessary for Delta(9)-THC-induced memory impairment.

Abstract

The results of recent in vitro studies have underscored the important role that activation of CB(1) receptors has on GABAergic activity in brain areas associated with memory. The primary purpose of this study was to test the hypothesis that the memory disruptive effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in vivo are mediated through GABAergic systems. Conversely, we also evaluated whether blocking CB(1) receptor signaling would alter memory deficits elicited by GABA agonists. The GABA(A) antagonist bicuculline and GABA(B) antagonist CGP 36742 were evaluated for their ability to ameliorate Delta(9)-THC-induced deficits in a mouse working memory Morris water maze task. Mice were also assessed in a T-maze task, as well as non-cognitive behavioral assays. Additionally, the effects of GABA(A) and GABA(B) agonists were assessed in either CB(1) (-/-) mice or wild type mice treated with the CB(1) antagonist SR 141716. Memory deficits resulting from 10 mg/kg Delta(9)-THC in the Morris water maze were completely reversed by bicuculline, though unaffected by CGP 36742. Bicuculline also blocked the disruptive effects of Delta(9)-THC in the T-maze, but failed to alter non-mnemonic effects of Delta(9)-THC. Although CB(1) (-/-) mice exhibited supersensitivity to muscimol-induced water maze deficits compared with wild type control mice, muscimol elicited virtually identical effects in SR 141716-treated and vehicle-treated wild type mice. This is the first demonstration of which we are aware showing that GABA(A) receptors may play a necessary role in Delta(9)-THC-induced memory impairment in whole animals.

Comparable studies

Other preclinical and animal studies on cannabis, most cited first.

Study Year Design Participants
Cognitive Impairment Induced by Delta9-tetrahydrocannabinol Occurs through Heteromers between Cannabinoid CB1 and Serotonin 5-HT2A Receptors Mice 2015 Preclinical study
Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). hMDR1- and hBCRP-transfected HEK293 cells and hMDR1- and hBCRP-MDCKII cells 2010 In vitro study
Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Mice prenatally exposed to THC, including conditional CB1R knockout mice 2020 Animal experimental study
Chronic cannabis promotes pro-hallucinogenic signaling of 5-HT2A receptors through Akt/mTOR pathway Mice exposed to chronic THC early in life 2018 Animal experimental study
Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain Spontaneously hypertensive rats (SHRs) and Wistar rats 2014 Animal experimental study

Citations in the library

Cited by 6

and 1 more in the library

Cites 4

Related reading

Explore topics

Cannabis