Titre du document / Document title

Perinatal Δ⁹-tetrahydrocannabinol exposure augmented the magnitude of motor inhibition caused by GABA_B, but not GABA_A, receptor agonists in adult rats

Auteur(s) / Author(s)

GARCIA-GIL L. ⁽¹⁾ ; DE MIGUEL R. ⁽¹⁾ ; ROMERO J. ⁽¹⁾ ; PEREZ A. ⁽¹⁾ ; RAMOS J. A. ⁽¹⁾ ; FERNANDEZ-RUIZ J. J. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Instituto Complutense de Drogodependencias, Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, ESPAGNE

Résumé / Abstract

We have extensively reported that A9-tetrahydrocannabinol (Δ⁹-THC) exposure results in changes in the adult functionality of dopaminergic neurons, in particular, mesotelencephalic pathways, although some changes are evident only after pharmacological challenges. In the present study, we have examined whether similar changes might be observed in γ-aminobutyric acid (GABA) activity, in particular, in those regions where cannabinoid receptors have been reported to be located in GABA-containing neurons. To this end, we first examined GABA content and glutamic acid decarboxylase (GAD) activity in several brain regions of adult male and female rats that had been perinatally exposed to Δ⁹-THC or oil. Δ⁹-THC exposure did not modify either GAD activity or GABA content in the ventral-tegmental area, nucleus accumbens, substantia nigra, caudate-putamen, and globus pallidus, thus suggesting no changes in the basal presynaptic activity of GABA-containing neurons. Second, we tested the motor response in the open-field test of these animals after a single injection of muscimol, a GABA_A receptor agonist, baclofen, a GABA_B receptor agonist, or vehicle. We observed that the motor inhibition caused by baclofen, in terms of decreased ambulation and stereotypy and increased inactivity, was more marked in magnitude in Δ⁹-THC-exposed males and females. This was not observed for the GABA_A receptor agonist, muscimol, indicating a receptor specificity. To extend this observation, we also examined whether the potential differences in the behavioral response found in the above experiment might be due to changes at the level of the efficiency of the activation of these receptors by measuring basal and baclofen-stimulated [³⁵S]-guanylyl-5'-O-(γ-thio)-triphosphate ([³⁵S]-GTPγS) binding in adult male and female rats that had been perinatally exposed to Δ⁹-THC or oil. However, our results were negative, because perinatal Δ⁹-THC exposure did not increase baclofen-stimulated [³⁵S]-GTPγS binding in the areas studied; in particular, in the substantia nigra, an area of interest for the interactions GABA_B receptor/cannabinoid receptor. Collectively, the present results indicate that although perinatal Δ⁹-THC did not produce any changes in GABA content and GAD activity in limbic and motor areas in adulthood, it did increase the behavioral response to GABA_B receptor agonists. However, this increase was not due to changes in GABA_B receptor activation of signal transduction mechanisms, as revealed the analysis of the percentage of stimulation by baclofen of [³⁵S]-GTPγS binding in the substantia nigra and other structures of males and females perinatally exposed to Δ⁹-THC.

Revue / Journal Title

Neurotoxicology and teratology   ISSN 0892-0362   CODEN NETEEC 

Source / Source

1999, vol. 21, n^o3, pp. 277-283 (32 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier Science, New York, NY, ETATS-UNIS  (1987) (Revue)

Mots-clés anglais / English Keywords

Drug of abuse ; Mechanism of action ; Toxicity ; Teratogenesis ; Central nervous system disease ; Oral administration ; Adult animal ; Rat ; GABA ; Gabaergic receptor A ; Gabaergic receptor B ; Pregnancy ; Lactation ; Cannabinoid ; Progeny ; Postnatal development ; Perinatal ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés français / French Keywords

Cannabinol(6a,7,8,10a-tétrahydro) ; Substance toxicomanogène ; Mécanisme action ; Toxicité ; Tératogenèse ; Système nerveux central pathologie ; Voie orale ; Animal adulte ; Rat ; GABA ; Récepteur gabaergique A ; Récepteur gabaergique B ; Gestation ; Lactation ; Cannabinoïde ; Descendance ; Développement postnatal ; Périnatal ; Rodentia ; Mammalia ; Vertebrata ;

Mots-clés espagnols / Spanish Keywords

Sustancia toxicomanógena ; Mecanismo acción ; Toxicidad ; Teratogenesis ; Sistema nervosio central patología ; Vía oral ; Animal adulto ; Rata ; GABA ; Receptor gabaminérgico A ; Receptor gabaminérgico B ; Gestación ; Lactación ; Canabinoide ; Descendencia ; Desarrollo postnatal ; Perinatal ; Rodentia ; Mammalia ; Vertebrata ;

Localisation / Location

INIST-CNRS, Cote INIST : 18910, 35400008531460.0080