The effects of chronic administration of tranylcypromine and rimonabant on behaviour and protein expression in brain regions of the rat.
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 (10 mg/kg) or rimonabant (2 mg/kg) were given for 14 days. 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.
School of Biomedical Sciences and Institute of Neuroscience, University of Nottingham, Nottingham NG7 2UH, UK. n_assareh@yahoo.com
Neda
N
Assareh
Maha M
MM
ElBatsh
Charles A
CA
Marsden
David A
DA
Kendall
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001362:Avoidance Learning; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D054314:Drug Inverse Agonism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000627:therapeutic use*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D015398:Signal Transduction / Q000187:drug effects; D014191:Tranylcypromine / Q000008:administration & dosage / Q000627:therapeutic use
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D008996:Monoamine Oxidase Inhibitors; D009419:Nerve Tissue Proteins; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D014191:Tranylcypromine; D000077285:Rimonabant