Neophobia and cortical and subcortical binding of the dopamine D2 receptor antagonist [3H]-raclopride.

The potential role of dopamine system in response to novelty was analysed using the selective dopamine D2 receptor antagonist, raclopride, in behavioral and biochemical assays, in rats (the open field test, and specific binding of [3H]-raclopride, within different brain structures measured with autoradiography). It was found that raclopride at a low dose (50 microg/kg, IP) caused anxiolytic-like effect (increased the anti-thigmotactic index), whereas at a higher dose (500 microg/kg, IP) produced general inhibitory influence, and decreased the anti-thigmotactic index. Analysis of the behavioral and biochemical results of the experiment revealed a significant negative correlation between the ligand binding in the substantia nigra pars reticulata (SNR), and the number of entries into the central sector of the open field (r=-0.

The role of neurosteroids in the anxiolytic,antidepressive- and anticonvulsive effects of selective serotonin reuptake inhibitors.

The introduction of SSRIs to the clinic was a turning point in the treatment of depression and related mental disorders. Nowadays, it is becoming more and more evident that SSRIs are equally effective in anxiety states and some types of epilepsy. However, the mechanism of their central action is not fully understood.

Rat behavior in two models of anxiety and brain [3H]muscimol binding: pharmacological, correlation, and multifactor analysis.

The contribution of GABAergic mechanisms to rat emotional behavior in two animal models of anxiety (open field test of neophobia and aversively conditioned freezing reaction), was confirmed by pharmacological analysis, using anxiolytic (midazolam) and anxiogenic (picrotoxin) compounds. Both substances are known to modulate GABA(A) receptors' activity in a positive or negative manner, respectively. It seemed, therefore, worthwhile to check whether the behavioral parameters measured in these animal models of anxiety correlate with [3H]muscimol binding (a highly selective GABA(A) receptor ligand) in different brain structures of nai;ve rats, with a view to establish the role of genetically determined expression of local GABA(A) receptors in the organization of rat emotional and motor behavior.

Lack of changes in cortical [3H]-muscimol binding in rats sensitized to nicotine-induced enhancement of dopamine metabolism.

It was proposed that chronic nicotine treatment may induce adaptive changes in GABAA receptors, thus leading to the attenuation of a GABAergic inhibition of dopaminergic neurons. This putative mechanism might underlie the sensitization to nicotine-induced increase in locomotor activity and dopamine metabolism; i.e.

The effects of central administration of physostigmine in two models of anxiety.

The effects of intracerebroventricular and intraseptal (the medial septum) administration of a prototypical acetylcholinesterase inhibitor (AChE-I), physostigmine, and a classic benzodiazepine midazolam on rat behavior in the open field test of neophobia and in the conditioned fear test (freezing reaction) were examined in rats. In the open field test of neophobia midazolam and physostigmine increased at a limited dose range, rat exploratory activity, after intracerebroventricular injection. Physostigmine produced in addition the hyperlocomotory effect.

Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems.

The influence of pentylenetetrazol (PTZ)-induced kindling of seizures on the rat emotional behavior, the brain monoamine turnover rate measured in vitro, and correlation between behavioral and biochemical parameters, were examined in rats. The repeated administration of PTZ (35 mg/kg, ip) evoked kindled seizures in rats (Stage 4 or 5 of clonic-tonic convulsions-maximum). PTZ kindling caused selective changes in the rat emotional behavior, present in some models of anxiety only (a decreased freezing time in the conditioned freezing test and a decreased spontaneous and aversively conditioned ultrasonic vocalization).

Antagonism of picrotoxin-induced changes in dopamine and serotonin metabolism by allopregnanolone and midazolam.

The effects of allopregnanolone and midazolam, given intracerebroventricularly, on the behavioral and biochemical effects of picrotoxin, were examined in a model of neurotoxin-induced seizures, in mice. After acute injections, midazolam (ED(50)=39.8 nmol) and allopregnanolone (ED(50)=11.