Increased locomotor response to amphetamine, but not other psychostimulants, in adult mice submitted to a low-protein diet.

Protein malnutrition results in a variety of brain dysfunctions, ultimately affecting cognitive functions. The effects of protein malnutrition in brain response to psychostimulants have been less studied in adult animals. We therefore aimed to study the response to psychoactive drugs on the locomotor activity (a behavior paradigm) of adult protein malnourished mice. Two-month-old mice were divided in two groups: (a) low-protein group (LP), which received 6% of protein diet, and (b) a control group that received a 25% of protein diet. After 3 months, they were tested for locomotor activity after an i.p. injection of one of psychoactive drugs: D-amphetamine (5.0 mg/kg), apomorphine (2.0 mg/kg), dizocilpine (0.25 mg/kg), or caffeine (30 mg/kg). Mice submitted to the LP diet presented prolonged induction of hyperlocomotion caused by amphetamine (about 350% between 90 and 180 min post drug injection as compared with well-nourished mice, p<0.01) but presented unaltered response to apomorphine, caffeine, and dizocilpine. These data point to altered catecholamine metabolism induced by protein restriction in adult mice. The results are discussed based on previous works, presenting theoretical hypotheses about the possible mechanisms involved in the present findings.

Guanosine selectively inhibits locomotor stimulation induced by the NMDA antagonist dizocilpine.

Guanosine has been shown to modulate glutamate system by stimulating astrocytic glutamate uptake. Recent evidence suggest that the locomotor effects of NMDA receptor antagonists, an animal model of schizophrenia, is associated with activation of non-NMDA glutamatergic receptors caused by increased glutamate release. The present work was undertaken to evaluate whether guanosine could have influence on the hyperlocomotion induced in mice by dizocilpine (MK-801), a NMDA antagonist. We also evaluated the effect of guanosine on the hyperlocomotion induced by the indirect dopamine agonist amphetamine, and by the non-selective adenosine receptor antagonist caffeine. Guanosine (7.5 mg/kg) produced an attenuation of about 60% on the hyperlocomotion induced by dizocilpine (0.25 mg/kg), whereas it did not affect the hyperlocomotion induced by amphetamine (5 mg/kg) or caffeine (30 mg/kg). Guanosine pre-treatment did not affect total spontaneous locomotion in all experiments. To test neuronal pathway selectivity, we evaluated MK-801 against guanosine in a working memory paradigm (spontaneous alternation task). Guanosine did not reverted the impairment caused by MK-801 in the spontaneous alternation test, and when administered alone also presented an amnesic effect. The results are discussed based on the current hypothesis of locomotor activation induced by the psychoactive drugs studied. Further studies are necessary to evaluate if guanosine could have clinical utility for the treatment of schizophrenia.