|Welcome Dr. Kendall! From which planet are you arriving??? |
Pharmacol Biochem Behav. 2011 Oct 20. [Epub ahead of print]
The effects of chronic administration of tranylcypromine and rimonabant on behaviour and protein expression in brain regions of the rat.
Assareh N, Elbatsh MM, Marsden CA, Kendall DA.
Recent findings indicate that CB1 receptor blockade might be relevant to the action of antidepressant drugs as inhibition of endocannabinoid function can increase synaptic availability of neurotransmitters; an effect also seen with chronic antidepressant drug treatment. Chronic treatments with established antidepressants also lead to raised brain BDNF levels. The aim of this study was to compare the effects of rimonabant (an inverse agonist/antagonist of CB1 receptors) with those of the antidepressant tranylcypromine (TCP), on behaviour and expression of BDNF/CREB signalling pathways in rat brain. Daily (i.p.) injections of vehicle or TCP (10mg/kg) or rimonabant (2mg/kg) were given for 14days. Locomotor activity (LMA) and a conditional emotional response (CER) were measured in addition to levels of BDNF and CREB/phospho-CREB, using immunoblotting, in the frontal cortex, hippocampus, striatum and cerebellum. The velocity of movement was increased significantly on the 3rd, but not 9th, day of TCP treatment versus vehicle-treated rats (p<0.05) while rimonabant had no effect. There were no significant changes in grooming or freezing behaviours after rimonabant or TCP compared to vehicle-treated rats. Rearing was significantly reduced by TCP treatment on the 3rd, but not 9th, day of treatment (p<0.001) while rimonabant had no effect. BDNF levels were significantly increased in the frontal cortex after TCP (p<0.05) but not by rimonabant. Neither TCP nor rimonabant significantly affected CREB or p-CREB expression. In conclusion, chronic administration of TCP to rats increased BDNF expression in the frontal cortex but no similar effect was observed with rimonabant indicating that rimonabant does not show antidepressant drug-like responses after chronic treatment.
Lipids Health Dis. 2011 Oct 28;10(1):194. [Epub ahead of print]
Adipose tissue endocannabinoid system gene expression: depot differences and effects of diet and exercise.
You T, Disanzo BL, Wang X, Yang R, Gong D.
Alterations of endocannabinoid system in adipose tissue play an important role in lipid regulation and metabolic dysfunction associated with obesity. The purpose of this study was to determine whether gene expression levels of cannabinoid type 1 receptor (CB1) and fatty acid amide hydrolase (FAAH) are different in subcutaneous abdominal and gluteal adipose tissue, and whether hypocaloric diet and aerobic exercise influence subcutaneous adipose tissue CB1 and FAAH gene expression in obese women. Methods: Thirty overweight or obese, middle-aged women (BMI=34.3+/-0.8 kg/m2, age= 59+/-1 years) underwent one of three 20-week weight loss interventions: caloric restriction only (CR, N=9), caloric restriction plus moderate-intensity aerobic exercise (CRM, 45-50% HRR, N=13), or caloric restriction plus vigorous-intensity aerobic exercise (CRV, 70-75% HRR, N=8). Subcutaneous abdominal and gluteal adipose tissue samples were collected before and after the interventions to measure CB1 and FAAH gene expression. Results: At baseline, FAAH gene expression was higher in abdominal, compared to gluteal adipose tissue (2.08+/-0.11 vs. 1.78+/-0.10, expressed as target gene/-actin mRNA ratio x 10-3, P<0.05). Compared to pre-intervention, CR did not change abdominal, but decreased gluteal CB1 (Delta=-0.82+/-0.25, P<0.05) and FAAH (Delta=-0.49+/-0.14, P<0.05) gene expression. CRM or CRV alone did not change adipose tissue CB1 and FAAH gene expression. However, combined CRM and CRV (CRM+CRV) decreased abdominal adipose tissue FAAH gene expression (Delta=-0.37+/-0.18, P<0.05). The changes in gluteal CB1 and abdominal FAAH gene expression levels in the CR alone and the CRM+CRV group were different (P<0.05) or tended to be different (P=0.10). Conclusions: There are depot differences in subcutaneous adipose tissue endocannabinoid system gene expression in obese individuals. Aerobic exercise training may preferentially modulate abdominal adipose tissue endocannabinoid-related gene expression during dietary weight loss.
Eur J Neurosci. 2011 Nov;34(9):1369-1377. doi: 10.1111/j.1460-9568.2011.07876.x.
Loss of striatal cannabinoid CB1 receptor function in attention-deficit?/?hyperactivity disorder mice with point-mutation of the dopamine transporter.
Castelli M, Federici M, Rossi S, De Chiara V, Napolitano F, Studer V, Motta C, Sacchetti L, Romano R, Musella A, Bernardi G, Siracusano A, Gu HH, Mercuri NB, Usiello A, Centonze D.
Clinica Neurologica, Dipartimento di Neuroscienze, Università Tor Vergata, Via Montpellier, Rome, Italy Fondazione Santa Lucia, Rome, Italy Behavioural Neuroscience Laboratory, CEINGE - Biotecnologie Avanzate, Naples, Italy Clinica Psichiatrica, Dipartimento di Neuroscienze, Università Tor Vergata, Rome, Italy Department of Pharmacology, Ohio State University, Columbus, OH, USA Dipartimento di Scienze Ambientali, Seconda Università di Napoli, Caserta, Italy.
Abnormal dopamine (DA) transmission in the striatum plays a pivotal role in attention-deficit/hyperactivity disorder (ADHD). As striatal DA signalling modulates the endocannabinoid system (ECS), the present study was aimed at investigating cannabinoid CB1 receptor (CB1R) function in a model of ADHD obtained by triple point-mutation in the dopamine transporter (DAT) gene in mice, making them insensitive to cocaine [DAT cocaine-insensitive (DAT-CI) mice]. DAT-CI mice had a marked hyperactive phenotype, and neurophysiological recordings revealed that the sensitivity of CB1Rs controlling GABA-mediated synaptic currents [CB1Rs((GABA)) ] in the striatum was completely lost. In contrast, CB1Rs modulating glutamate transmission [CB1Rs((Glu)) ], and GABA(B) receptors were not affected in this model of ADHD. In DAT-CI mice, the blockade of CB1R((GABA)) function was complete even after cocaine or environmental manipulations activating the endogenous DA-dependent reward system, which are known to sensitize these receptors in control animals. Conversely, the hedonic property of sucrose was intact in DAT-CI mice, indicating normal sweet perception in these animals. Our results point to CB1Rs as novel molecular players in ADHD, and suggest that therapeutic strategies aimed at interfering with the ECS might prove effective in this disorder.