Behavioural brain research
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Recent evidence indicates that adenosine A2A receptors modulate the activity of striatal neurons, and that antagonists of this receptor may have actions in various animal models related to motor function. Four experiments were conducted to study the effects of systemic injections of the adenosine A2A antagonist KF17837 on the behavioral effects produced by repeated administration of the dopamine (DA) antagonist haloperidol. In the first two experiments, it was shown that repeated 0.5 mg/kg haloperidol severely suppressed open-field locomotor activity, and that KF17837 (0.0-20.0 mg/kg) did not significantly increase open-field locomotor activity. ⋯ The fourth experiment demonstrated that i.p. injections of KF17837 (0.0-20.0 mg/kg) also suppressed haloperidol-induced tremulous jaw movements. Taken together, the results of these experiments indicate that adenosine A2A antagonism can reverse the locomotor suppression and tremulous movements induced by DA antagonism. This profile of activity is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in an antiparkinsonian effect in animal models.
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Comparative Study
Stereotypies in caged parrots, schizophrenia and autism: evidence for a common mechanism.
Spontaneously occurring abnormal behaviors in animals have recently received considerable attention, both in veterinary medicine and as a potential model for abnormal behavior in several human mental disorders. Stereotypies are abnormal repetitive, unvarying, and functionless behaviors that are often performed by captive and domesticated animals housed in barren environments. They closely resemble the stereotypies of autistic and mentally retarded patients, stereotypies of unmedicated chronic schizophrenic patients, certain classes of simple tic in Tourette's syndrome, and several drug-induced behaviors. ⋯ These results, therefore, suggest that the pharmacological treatment of stereotypies in veterinary medicine based on the assumption that they are equivalent to human Obsessive-Compulsive Disorder may be inappropriate. As stereotypies in captive animals develop in response to the captive environment, these results also emphasize the role that the environment may play in eliciting or exacerbating stereotypy in human patients. Finally, by parallel to human patients, there is a potential psychological distress in animals showing these behaviors.
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Comparative Study
Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice.
This study investigated the involvement of NMDA receptors and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like effects of zinc in the forced swimming test (FST). The immobility times in the FST and in the tail suspension test (TST) were reduced by zinc chloride (ZnCl(2), 30 and 10-30 mg/kg intraperitoneal (i.p.), respectively). The doses active in the FST and TST reduced locomotor activity in an open-field. ⋯ The immobility time of mice treated with ZnCl(2)+MK-801 was not different from the result obtained with ZnCl(2) or MK-801 alone, but ZnCl(2)+imipramine had a greater effect in the FST than administration of either drug alone. Pre-treatment of animals with a sub-threshold dose of ZnCl(2) prevented the anti-immobility effect of MK-801, ketamine, GMP, L-arginine or N(G)-nitro-L-arginine (L-NNA), but did not alter the effect of imipramine or fluoxetine. Taken together, the results demonstrate that zinc produced an antidepressant-like effect that seems to be mediated through its interaction with NMDA receptors and the L-arginine-NO pathway.
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Comparative Study
Waking selective neurons in the posterior hypothalamus and their response to histamine H3-receptor ligands: an electrophysiological study in freely moving cats.
Neurons which discharge selectively during waking (waking selective) have been found in the tuberomamillary nucleus (TM) and adjacent areas of the posterior hypothalamus. Although they share some electrophysiological properties with aminergic neurons, there is no direct evidence that they are histaminergic. We have recorded from posterior hypothalamic neurons during the sleep-wake cycle in freely moving cats, and investigated the effects on waking selective neurons of specific ligands of histaminergic H3-receptors, which autoregulate the activity of histaminergic neurons. ⋯ Moreover, the effect of the antagonist was reversed by the agonists and vice versa. In contrast, "waking-related" neurons were unaffected by these H3-receptor ligands. These data provide evidence for the histaminergic nature of "W-on" neurons and their role in cortical desynchronization during waking, and highlight the heterogeneity of posterior hypothalamic neuronal populations, which might serve different functions during the wakefulness.
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Comparative Study
Depressive-like behavioral alterations and c-fos expression in the dopaminergic brain regions in WAG/Rij rats with genetic absence epilepsy.
Wistar derived inbred line, the WAG/Rij rats, genetically absence epilepsy prone and their normal counterparts, outbred Wistar rats, were compared in respect to differences in behavior, in acute and chronic antidepressant imipramine treatment and in the immediate early gene c-fos expression in the brain regions induced by forced swimming test procedure. The WAG/Rij rats as compared with Wistar rats were found to exhibit decreased activity in the open field test, increased immobility in the forced swimming test and decreased sucrose intake (anhedonia). Interline differences indicating increased anxiety in the WAG/Rij rats were not revealed in the light-dark choice, social interaction and elevated plus-maze tests. ⋯ Results suggest that WAG/Rij rats are prone to adopt passive strategies of behavior in stressful situations, and so in this certain aspect this strain might be regarded as new experimental (genetic) model of depressive-like (passive) behavior accompanying absence epilepsy. Further testing this hypothesis is proceeding. This putative model could be used for the investigation of neurobiological basis and mechanisms of such "double pathology" and for the examination of new concepts of its therapy.