venlafaxine (Effexor)
The antinociceptive effect of tramadol-venlafaxine combination on the paw withdrawal threshold in a rat model of neuropathic pain.

Uyar M, Onal A, Uyar M, Dogru A, Soykan N.

Pain Clinic, Department of Anesthesiology, Bornova, Izmir, Turkey. meltem med.ege.edu.tr

The combination of venlafaxine and tramadol was compared with the single use of these agents to investigate the antinociceptive effect on paw withdrawal latency (PWL) to paw pressure in rats with neuropathic pain. Rats were divided into 4 groups: group 1 received saline (0.2 ml i.p.); group 2 received venlafaxine (22 mg/kg i.p.); group 3 received tramadol (20 mg/kg i.p.); and group 4 received venlafaxine + tramadol. No statistically significant changes were observed in the saline and venlafaxine groups with respect to PWL in the lesioned paw. However, tramadol produced a significant antinociceptive effect on the lesioned paw at 30 min compared with the saline and venlafaxine groups. A more potent antinociceptive effect was observed in the tramadol + venlafaxine group, beginning at 60 min and lasting for 1 h. The combination of venlafaxine + tramadol was more effective in increasing the pain threshold in this animal model of neuropathic pain than either of these drugs administered alone. (c) 2003 Prous Science. All rights reserved.

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Effexor, Effexor XR

venlafaxine (Effexor)
Evidence for an antihyperalgesic effect of venlafaxine in vincristine-induced neuropathy in rat.

Marchand F, Alloui A, Pelissier T, Hernandez A, Authier N, Alvarez P, Eschalier A, Ardid D.

Laboratoire de Pharmacologie Medicale, Faculte de Medecine, E 9904 INSERM/UdA, 63001 Clermont-Ferrand Cedex 1, France.

Venlafaxine, a new antidepressant with fewer side effects, could be of interest to reduce neuropathic pain following antineoplasic drug treatment. In the present study, we demonstrated that venlafaxine inhibits hyperalgesia in a new rat model of neuropathy induced by the antineoplasic drug vincristine, and exerts its effect preferentially via supraspinal and spinal mechanisms.

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Effexor, Effexor XR

venlafaxine (Effexor)
Role of neuropeptides in antidepressant and memory improving effects of venlafaxine.

Nowakowska E, Kus K, Bobkiewicz-Kozlowska T, Hertmanowska H.

Department of Pharmacology, Karol Marcinkowski University of Medical Sciences, Rokietnicka 5A, PL 60-806 Poznan, Poland.

The aim of this study has been to investigate the effects of vasopressin and oxytocin on antidepressive and memory improving effects of venlafaxine. Male Wistar rats weighing 180-200 g were used in the study. Venlafaxine (20 mg/kg) was administered po 30 min before the test once, and for 7 and 14 days in the chronic experiments. Oxytocin (1 microg/kg) ip and vasopressin (1 microg/kg) sc were administered only once on the test day, 60 min before the tests. The animals were subjected to Porsolt's test for testing antidepressant activity, and their memory functions (working and spatial memory) were evaluated in the maze test and Morris Water Maze test. Antidepressant effects of venlafaxine could be observed already after single drug administration and the effect was maintained during 7 days of drug administration. Oxytocin also exhibited antidepressant activity, and concurrent administration of venlafaxine and oxytocin helped to maintain antidepressant activity of venlafaxine. Vasopressin was devoid of antidepressant action, yet concurrent administration of vasopressin and venlafaxine did not suppress antidepressant activity of the latter. In the chronic experiment, there was no shortening of passive swimming time. Venlafaxine improved memory in the labyrinth test and in the spatial memory test, whereas oxytocin did not affect memory of the tested animals. Joint administration of venlafaxine and oxytocin did not produce memory improving effect observed after administration of venlafaxine only. Vasopressin improved memory and joint administration of venlafaxine and vasopressin maintained the memory improving effect induced by vasopressin. The regulatory role of neuropeptides and new antidepressant drugs, e.g. venlafaxine in mood status and memory functions may depend on the interactions between monoaminergic and neuropeptidergic systems.

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Effexor, Effexor XR

venlafaxine (Effexor)
Does combined treatment with novel antidepressants and a dopamine D3 receptor agonist reproduce cocaine discrimination in rats?

Filip M, Papla I.

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow. filip if-pan.krakow.pl

It is established that dopamine (DA) neurotransmission plays a critical role in the behavioral (e.g. discriminative stimulus) effects of cocaine in rodents. Nonetheless, research has also demonstrated that reciprocal signaling between DA and monoamine neurotransmitters, i.e. serotonin (5-HT) and norepinephrine (NE) has important implication for understanding the actions of cocaine. The present study was focussed on the ability of novel antidepressant drugs (milnacipram, reboxetine and venlafaxine), which affect either NE or both 5-HT and NE reuptake mechanism, to alter (enhance or antagonize) the discriminative stimulus effects of cocaine. Moreover, we investigated if the combined treatment with those drugs and a DA D3 receptor agonist (pramipexole) could reproduce cocaine discrimination. Male Wistar rats were trained to discriminate cocaine (10 mg/kg, ip) from saline (ip) in a two-choice, water-reinforced fixed-ratio 20 drug discrimination paradigm. Given alone, none of antidepressant drugs induced substitution for the cocaine-lever responses. Pramipexole (0.25 mg/kg) produced a partial substitution for cocaine (i.e. 43-52% cocaine-lever responding). In combination experiments, milnacipram (10 mg/kg) or reboxetine (10 mg/kg) given with submaximal doses of cocaine (1.25-5 mg/kg) did not affect the cocaine dose-response curve or its ED50 values. Venlafaxine (10 mg/kg) given in combination with submaximal doses of cocaine (0.6-5 mg/kg) produced significant enhancement of cocaine discrimination with a leftward shift in the cocaine dose-response curve and a decrease in its ED50 value. Pretreatment with either milnacipram (10 mg/kg) or reboxetine (10 mg/kg) failed to modulate the partial substitution evoked by pramipexole (0.25 mg/kg). On the other hand, venlafaxine (10 mg/kg) given in combination with a submaximal dose of pramipexole (0.25 mg/kg), which separately elicited 16 and 42% the cocaine-lever responses, produced significant enhancement of cocaine discrimination (up to 99% of the drug-lever responding). These results indicate that the discriminative stimulus effects of cocaine in rats can be enhanced by venlafaxine or mimicked by the combination with this antidepressant drug and the DA D3 receptor agonist. This finding, together with the recent data reporting the lack of rewarding properties of venlafaxine and the attenuation of morphine dependence and withdrwal signs in rats by the drug, may indicate a possible therapeutic use of this antidepressant in cocaine abuse.

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Effexor, Effexor XR

venlafaxine (Effexor)
Effects of venlafaxine on extracellular 5-HT, dopamine and noradrenaline in the hippocampus and on peripheral hormone concentrations in the rat in vivo.

Piacentini MF, Clinckers R, Meeusen R, Sarre S, Ebinger G, Michotte Y.

Department of Human Physiology and Sportsmedicine, Vrije Universiteit Brussel, Brussels, Belgium.

The purpose of the present study was to study the effect of an acute dose of the serotonin (5-HT) - noradrenaline (NA) reuptake inhibitor venlafaxine on extracellular concentrations of 5-HT, NA and dopamine (DA) in the hippocampus and on the peripheral hormone concentrations in freely moving rats. Blood obtained from a catheter placed in the vena femoralis was analyzed for adrenocorticotropin (ACTH), beta-endorphins, prolactin (PRL), growth hormone (GH) and cortisol. Collections are referred to pre and post injection of 20 mg/kg of venlafaxine. Extracellular hippocampal NA and 5-HT as determined with in vivo microdialysis increased significantly after drug injection. PRL and ACTH were significantly affected by the drug. At the selected dose venlafaxine is able to increase the release of 5-HT but also of NA in rat hippocampus. Due to the dual reuptake properties of the drug and the functional interconnection of the NA and the 5-HT systems, the observed effects on peripheral hormones are possibly mediated by a combined action of these 2 systems.

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Effexor, Effexor XR