ABSTRACT
The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic α1-AR activation modulates glutamate and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic α1-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that α1-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an α1-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of α1-ARs persists after a 7-day withdrawal period. In contrast, the modulation of α1-ARs on GABA neurotransmission, shown by decreases in IPSCs' amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that α1-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of α1-ARs' function on glutamate release and protein kinase C (PKC) activation. α1-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.
Subject(s)
Cocaine/metabolism , Dopaminergic Neurons/metabolism , Glutamic Acid/metabolism , Receptors, Adrenergic, alpha-1/metabolism , Ventral Tegmental Area/cytology , Ventral Tegmental Area/metabolism , gamma-Aminobutyric Acid/metabolism , Action Potentials/drug effects , Animals , Cocaine/administration & dosage , Cocaine-Related Disorders/etiology , Cocaine-Related Disorders/metabolism , Disease Models, Animal , Dopaminergic Neurons/drug effects , Male , Models, Biological , Patch-Clamp Techniques , Presynaptic Terminals/metabolism , Rats , Signal Transduction/drug effectsABSTRACT
Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.
Subject(s)
Adult , Humans , Male , Acetylcholine/pharmacology , Cardiovascular Agents/pharmacology , Hand/blood supply , Nitroprusside/pharmacology , Phenylephrine/pharmacology , Transcutaneous Electric Nerve Stimulation/methods , Analysis of Variance , Blood Glucose , Cholesterol/blood , Erythrocyte Count , Leukocyte Count , Lipoproteins, HDL/blood , Triglycerides/blood , Urea/blood , Vasoconstriction/drug effects , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Veins/drug effectsABSTRACT
resumen Se describen tres casos clínicos de Síndrome Doloroso Regional Complejo Tipo 1, cuya denominación anterior era distrofia simpático refleja.Se analizaron los síntomas y signos para lograr un diagnóstico positivo y los exámenes complementarios solicitados en vistas a sostener el diagnóstico. Se mostraron los resultados del tratamiento destacándose la alta efectividad de nitroglicerina en parches transdérmicos.
summary We described three clinical cases with Complex Regional Pain Syndrome type 1, previously named Reflex Sympathetic Dystrophy, the symptoms and signs were analyzed looking for the diagnosis as well as the complementary studies needed to support it. Finally we showed the efficacy of the treatment with transdermic patches of nitro-glycerine, reaching very good and excellent results.
resumo Descreven-se 3 casos clínicos de Síndrome e Dolorosa Complexa Tipo 1, cuja denominação anterior era Distrofia Simpático Reflexa. Se analisaram os sintomas e sinais para chegar à um diagnóstico positivo e os exames complementares solicitados com vistas a sustentar o diagnóstico. Mostrar-se os resultados do tratamento destacando-se a alta efetividade da Nitroglicerina em adesivos transdérmicos.