Effects of long-term ganglioside GM1 administration on a new discriminative avoidance test in normal adult mice.

The beneficial effects of monosialoganglioside GM1 (GM1) on learning and memory have been detected mostly in animals presenting genetic, lesion-induced or age-related memory deficits. The present study was carried out to investigate the effects of GM1 on the discriminative avoidance behavior of normal adult mice. EPM-M1 male mice were treated daily IP with 50 mg/kg GM1 or saline for 14 days. The discriminative avoidance conditioning was performed on day 15 in a modified elevated plus-maze. In one of the enclosed arms, the animals received aversive stimulation (light and noise). Tests were performed on days 20, 25 and 30 (tests 1, 2 and 3). The time the animals spent in each of the enclosed arms was recorded. In tests 1 and 2, GM1-treated mice spent less time in the aversive arm in comparison to the non-aversive enclosed arm. On the other hand, control animals spent a shorter time in a aversive arm only in test 1. The results suggest that the beneficial effects of GM1 on learning and memory can be observed in normal animals as well.

Repeated monosialoganglioside administration attenuates behavioral sensitization to amphetamine.

The effects of repeated monosialoganglioside (GM1) administration on amphetamine-induced behavioral sensitization were studied using locomotion frequency of mice observed in an open-field as an experimental parameter. GM1 (30 mg/kg, once a day for 7 days) did not modify mouse behavior per se but decreased the hyperlocomotion of mice repeatedly treated with amphetamine (3.0 mg/kg, once a day for 7 days, 30 min after GM1 injection). GM1 acutely administered 30 min before amphetamine did not modify the increase in locomotion frequency induced by acute amphetamine administration. These results agree with previous reports that gangliosides treatment may affect synaptic-plasticity, modifying the induction of the adaptive changes following drug-treatment.

Monosialoganglioside attenuates the excitatory and behavioural sensitization effects of ethanol.

The effects of long-term monosialoganglioside GM1 treatment on the acute excitatory effects of ethanol and behavioural sensitization to this effect were studied, using locomotion frequency of mice observed in an open field as an experimental parameter. GM1 (30 mg/kg, once a day, for 21 days) did not modify mouse behaviour but decreased both the acute excitatory (1.8 g/kg) and the behavioural sensitization effects of ethanol (1.8 g/kg, once a day for 21 days, 30 min after GM1 injections). GM1 administered acutely 30 min or 24 h before ethanol did not modify the ethanol-induced increase in locomotion frequency. These results agree with previous reports in which ganglioside treatment modified both dopaminergic plasticity and other behavioural and biochemical effects of ethanol.

Antinociceptive effect of purine nucleotides.

The antinociceptive effect of purine nucleotides administered systematically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10, of 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that antinociceptive effect of adenine nucleotides is mediated by adenosine.

Antinociceptive effect of purine nucleotides

The antinociceptive effect of purine nucleotides administered systemically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P1 (caffeine, 5, 10 or 30 mg/kg); theophylline, 10 mg/kg) or purinergic P2 receptors (suramin, 100 mg/kg; Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that the antinociceptive effect of adenine nucleotides is mediated by adenosine.