Differential effects of Δ9-tetrahydrocannabinol dosing on correlates of schizophrenia in the sub-chronic PCP rat model

Autor: Alex A. Martinez, Alexandre Seillier, Andrea Giuffrida
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Cannabinoid receptor
Dopamine
Social Sciences
Phencyclidine
Biochemistry
0302 clinical medicine
Catecholamines
Animal Cells
Medicine and Health Sciences
Psychology
Drug Interactions
Dronabinol
Amines
Neurons
Mammals
education.field_of_study
Multidisciplinary
Animal Behavior
Organic Compounds
Drugs
Eukaryota
Neurochemistry
Neurotransmitters
Animal Models
Endocannabinoid system
Lipids
3. Good health
Ventral tegmental area
Chemistry
medicine.anatomical_structure
Experimental Organism Systems
Animal Sociality
Physical Sciences
Vertebrates
Medicine
Cellular Types
Neurochemicals
medicine.drug
Research Article
Signal Transduction
medicine.medical_specialty
Psychosis
Biogenic Amines
Polyunsaturated Alkamides
Science
Population
Arachidonic Acids
Nucleus accumbens
Motor Activity
Research and Analysis Methods
Rodents
03 medical and health sciences
Neurochemical
Model Organisms
Internal medicine
mental disorders
Mental Health and Psychiatry
medicine
Animals
Rats
Wistar
education
Pharmacology
Behavior
Glycogen Synthase Kinase 3 beta
business.industry
Cannabinoids
Organic Chemistry
Ventral Tegmental Area
Chemical Compounds
Organisms
Biology and Life Sciences
Cell Biology
medicine.disease
Hormones
030227 psychiatry
Rats
Disease Models
Animal
Endocrinology
Cellular Neuroscience
Amniotes
Schizophrenia
Animal Studies
business
Zoology
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Neuroscience
Endocannabinoids
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 3, p e0230238 (2020)
ISSN: 1932-6203
Popis: Social withdrawal in the sub-chronic phencyclidine (PCP) rat model, a behavioral correlate of the negative symptoms of schizophrenia, results from deficits in brain endocannabinoid transmission. As cannabis intake has been shown to affect negatively the course and expression of psychosis, we tested whether the beneficial effects of endocannabinoid-mediated CB1 activation on social withdrawal in PCP-treated rats (5 mg/kg, twice daily for 7 days)also occurred after administration of Δ9-tetrahydrocannabinol (THC; 0.1, 0.3, 1.0 mg/kg, i.p.). In addition, we assessed whether THC affected two correlates of positive symptoms: 1) motor activity induced by d-amphetamine (0.5 mg/kg, i.p.), and 2) dopamine neuron population activity in the ventral tegmental area (VTA). After the motor activity test, the brains from d-amphetamine-treated animals were collected and processed for measurements of endocannabinoids and activation of Akt/GSK3β, two molecular markers involved in the pathophysiology of schizophrenia. In control rats, THC dose-dependently produced social interaction deficits and aberrant VTA dopamine neuron population activity similar to those observed in PCP-treated animals. In PCP-treated rats, only the lowest dose of THC reversed PCP-induced deficits, as well as PCP-induced elevation of the endocannabinoid anandamide (AEA) in the nucleus accumbens. Last, THC activated the Akt/GSK3β pathway dose-dependently in both control and PCP-treated animals. Taken together, these data suggest that only low doses of THC have beneficial effects on behavioral, neurochemical and electrophysiological correlates of schizophrenia symptoms. This observation may shed some light on the controversial hypothesis of marijuana use as self-medication in schizophrenic patients.
Databáze: OpenAIRE
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