Blockade of adenosine and dopamine receptors inhibits the development of rapid tolerance to ethanol in mice

Abstract

Our results suggest that the rapid tolerance to ethanol-induced motor impairment in mice may be modulated by adenosine A1 receptors and dopamine D1 receptors.

Activation of Adenosine A1 Receptors Reduces Anxiety-Like Behavior During Acute Ethanol Withdrawal (Hangover) in Mice

“…In rodents, many studies using selective adenosine receptor agonists and antagonists have consistently demonstrated that adenosine receptors, localized in brain areas essential for motor control such as striatum, the cerebellum, and the motor cortex, are the primary site where adenosine modulates the incoordination induced by ethanol (Meng and Dar, 1995;Barwick and Dar, 1998;Dar, 2001). Additionally, we have recently demonstrated that the blockade of adenosine receptors inhibits the development of rapid tolerance to ethanol-induced motor impairment in mice (Batista et al, 2005).…”

“…In humans, the nonselective adenosine receptor antagonist caffeine reduces sleepiness and psychomotor performance impairment produced by moderate-to-high ethanol doses (Franks et al, 1975;Fillmore and Vogel-Sprott, 1995;Liguori and Robinson, 2001;Drake et al, 2003). In rodents, adenosine receptors seem to modulate some of the pharmacological properties of ethanol, such as sedative/ hypnotic effects (El Yacoubi et al, 2003), motor incoordination (Meng and Dar, 1995;Barwick and Dar, 1998;Dar, 2001), and development of rapid tolerance to ethanolinduced motor impairments (Batista et al, 2005).…”

Ethanol Interference on Adenosine System

“…A possible mechanism of the final response of the dimerized activation of these receptors is that ethanol desensitizes receptors linked to the stimulatory G protein ( subunit), modulating the coupling of D 2 with the AC pathway, which may be related to PKA (Yao et al, 2001;Batista et al, 2005). Inoue et al (2007) found that co-activation of A 2A and D 2 mediates the transient interaction between nicotine and ethanol, showing an indirect relationship with the cholinergic system, where the use of antagonists of this co-activation can prevent, mitigate or even reverse the use of smoke and ethanol.…”

The effects of adenosine antagonists on distinct aspects of motivated behavior: interaction with ethanol and dopamine depletion

“…Thus, the effect size for caffeine in this parameter is greater than for theophylline (see table 2). While low to moderate doses of caffeine (3-30 mg/kg) have demonstrated not to produce motor incoordination in mice in the rotarod [22,44], the present results on moderate to high doses of caffeine are in agreement with a study that evaluated the stumbling frequency in the holeboard test as a measure of motor coordination after moderate to high doses of caffeine (30-120 mg/kg), and demonstrated a dose-dependent increase in stumbling frequency [25]. Our data on theophylline are also consistent with a previous study showing that intraventricular administration of theophylline (150 µg/5µl) in mice did not affect endurance on the rotarod [45].…”

“…Although ethanol is generally classed as a sedative-hypnotic and caffeine is considered to be a minor stimulant, both drugs are able to stimulate locomotor activity in rodents at some dose [43][44][45][46][47][48] , typically with bell-shaped (or inverted-u) dose response functions. Rodents (more in mice than rats)…”