Thymoquinone Inhibition of Acquisition and Expression of Alcohol-Induced Behavioral Sensitization

Abstract

Repeated low doses of alcohol have been shown to progressively enhance locomotor activity in mice, and this phenomenon is designated as behavioral sensitization. Thymoquinone, a major active component of Nigella sativa oil has been investigated in a number of studies for its neuroprotective effects against a variety of ailments. This study was conducted to explore the therapeutic potential of thymoquinone on the acquisition and expression of alcohol-induced behavioral sensitization. Mice treated with alcohol (2.2 g/kg/day) or saline for 13 days and subsequently challenged with an acute alcohol dose (2.2 g/kg) 5 days later were orally administered acute doses of thymoquinone (10, 20 and 30 mg/kg). Thymoquinone subacute treatment with all doses throughout alcohol exposure significantly inhibited both the development and expression phases of alcohol behavioral sensitization in a dose-dependent manner. However, acute treatment with thymoquinone (30 mg/kg) only reversed the expression phase of sensitization. These findings are explained in terms of the known GABA promoting action of thymoquinone in relation to the motive circuit within the limbic component of the basal ganglia. It is concluded that thymoquinone may be a potential therapeutic option for the treatment and prevention of alcohol induced behavioral sensitization.

Microinjection of histone deacetylase inhibitor into the ventrolateral orbital cortex potentiates morphine induced behavioral sensitization

“…Repeated or even a single exposure to drugs of abuse can cause long-lasting behavioral sensitization which manifests as a progressive and enduring enhancement in the behavioral and neurochemical effects. (Guegan et al, 2015;Khan et al, 2015;Vanderschuren and Kalivas, 2000;Vanderschuren et al, 2001). Emerging evidence suggests that epigenetic modifications are suspected to participate in drug-induced behavioral sensitization (Renthal and Nestler, 2008;Weaver et al, 2004;Wong et al, 2011), but the concrete mechanism remains unclear.…”

“…The development phase is indicative of transient neuronal maladaptive alterations occurring during the acquisition of sensitization and the expression phase reflects neuronal adaptive alterations evoked by drug exposure. The transfer phase is the inter phase between development and expression Khan et al, 2015;King et al, 2000). Repeated or even a single exposure to drugs of abuse can cause long-lasting behavioral sensitization which manifests as a progressive and enduring enhancement in the behavioral and neurochemical effects.…”

“…One of the major clinical challenge of opiate addiction is its persistence even after long periods of drug abstinence, which is highlighted by high rates of drug relapse. Behavioral sensitization is a long-lasting form of neuronal plasticity that plays a key role in certain aspects of drug addiction such as drug-seeking behavior and relapse (Guegan et al, 2015;Khan et al, 2015;Vanderschuren and Kalivas, 2000;Vanderschuren et al, 2001). The behavioral sensitization phenomenon has been confirmed as a very useful model for studying the mechanisms underlying addiction.…”

A review of Neuropharmacology Effects ofNigella sativaand Its Main Component, Thymoquinone

“…) is known to be an active component in N. sativa seeds and contributes to the most of pharmacological effects of the plant such as anticonvulsant activity (Hosseinzadeh et al ., ), antioxidant (Hosseinzadeh et al ., ), anti‐inflammatory (Amin and Hosseinzadeh, ), antibacterial, and antifungal activity (Ziaee et al ., ; Forouzanfar et al ., ; Dey et al ., ), but it seems other compounds in the seeds have synergistic effects, and the combination of all constituents is necessary for N. sativa pharmacological activities (Paarakh, ). Recently, it has been shown that TQ could inhibit acquisition and expression of alcohol‐induced behavioral sensitization in mice (Khan et al ., ). There are numerous drugs in traditional medicine for curing various central nervous system (CNS) disorders.…”

Timokinonun izoproterenol ile indüklenen sıçan aortu üzerindeki sitoprotektif etkilerinin değerlendirilmesi

“…Rats were given subcutaneous (sc) 100 mg/kg depending on their body weight 15 . Thymoquinone (274666-5G, Purity ≥98%, Sigma-Aldrich Co. USA) 20 mg/kg intragastric (ig) was administered by dissolving in olive oil 16 . At the end of the experimental period, the animals were killed by decapitation under intraperitoneal ketamine (75 mg/kg) + xylazine (10 mg/kg) anesthesia.…”