Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes
| Autor: | John F. Cryan, Ted Dinan, Emilie Petit, John L. Waddington, Niamh Clarke, Orna Tighe, Lieve Desbonnet, Jeremy Walsh, Colm M. P. O’Tuathaigh, Gerard Clarke, Joseph A. Gogos, Claire O'Leary, Maria Karayiorgou |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Reflex
Startle medicine.medical_treatment Schizophrenia/enzymology Swimming/psychology Anxiety Pharmacology COMT inhibitor Nitrophenols Mice chemistry.chemical_compound 0302 clinical medicine Nitrophenols/pharmacology Reflex Startle/drug effects Pharmacology (medical) Enzyme Inhibitors Benzophenones/pharmacology Chromatography High Pressure Liquid Prepulse inhibition Pain Measurement Enzyme Inhibitors/pharmacology Mice Knockout Biogenic Monoamines/metabolism 3. Good health Cannabinoids/pharmacology Psychiatry and Mental health Phenotype Schizophrenia Schizophrenic Psychology Morpholines/pharmacology Psychology Naphthalenes/pharmacology medicine.drug Psychosis Benzoxazines/pharmacology Morpholines Anxiety/psychology Catechol O-Methyltransferase/genetics Naphthalenes Catechol O-Methyltransferase behavioral disciplines and activities Benzophenones 03 medical and health sciences Dopamine mental disorders medicine Animals Biogenic Monoamines Social Behavior Alleles Swimming Cannabinoid Receptor Agonists Catechol-O-methyl transferase Cannabinoids fungi Catechol O-Methyltransferase Inhibitors Cyclohexanols medicine.disease Benzoxazines 030227 psychiatry Mice Inbred C57BL chemistry Endophenotype Cannabinoid Receptor Agonists/pharmacology Tolcapone Cannabinoid Cyclohexanols/pharmacology Pain Measurement/drug effects 030217 neurology & neurosurgery |
| Zdroj: | The International Journal of Neuropsychopharmacology; Vol 15 O'Tuathaigh, C M P, Clarke, G, Walsh, J, Desbonnet, L, Petit, E, O'Leary, C, Tighe, O, Clarke, N, Karayiorgou, M, Gogos, J A, Dinan, T G, Cryan, J F & Waddington, J L 2012, ' Genetic vs. pharmacological inactivation of COMT influences cannabinoid-induced expression of schizophrenia-related phenotypes ', International Journal of Neuropsychopharmacology, vol. 15, no. 9, pp. 1331-1342 . https://doi.org/10.1017/S1461145711001581 |
| ISSN: | 1469-5111 |
| DOI: | 10.1017/S1461145711001581 |
| Popis: | Catechol-O-methyltransferase (COMT) is an important enzyme in the metabolism of dopamine and disturbance in dopamine function is proposed to be central to the pathogenesis of schizophrenia. Clinical epidemiological studies have indicated cannabis use to confer a 2-fold increase in risk for subsequent onset of psychosis, with adolescent-onset use conveying even higher risk. There is evidence that a high activity COMT polymorphism moderates the effects of adolescent exposure to cannabis on risk for adult psychosis. In this paper we compared the effect of chronic adolescent exposure to the cannabinoid WIN 55212 on sensorimotor gating, behaviours related to the negative symptoms of schizophrenia, anxiety- and stress-related behaviours, as well as ex-vivo brain dopamine and serotonin levels, in COMT KO vs. wild-type (WT) mice. Additionally, we examined the effect of pretreatment with the COMT inhibitor tolcapone on acute effects of this cannabinoid on sensorimotor gating in C57BL/6 mice. COMT KO mice were shown to be more vulnerable than WT to the disruptive effects of adolescent cannabinoid treatment on prepulse inhibition (PPI). Acute pharmacological inhibition of COMT in C57BL/6 mice also modified acute cannabinoid effects on startle reactivity, as well as PPI, indicating that chronic and acute loss of COMT can produce dissociable effects on the behavioural effects of cannabinoids. COMT KO mice also demonstrated differential effects of adolescent cannabinoid administration on sociability and anxiety-related behaviour, both confirming and extending earlier reports of COMT×cannabinoid effects on the expression of schizophrenia-related endophenotypes. |
| Databáze: | OpenAIRE |
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