Role of neurochemical mechanisms of the caudate nucleus in different models of anxiety in rats

Abstract

Microinjections of dopamine, apomorphine, and GABA to the dorsal part of the caudate nucleus decreased the level of anxiety in an illuminated platform avoidance task in rats, while sulpiride and picrotoxin increased it. Intrastriatal injection of serotonin, glutamic acid, yohimbine, and phenylephrine reduced anxiety in threatening situation, but not in the illuminated platform avoidance task. It is suggested that emotional states associated with different kinds of stress are realized through diverse neurochemical systems of the caudate nucleus neuronal network.Key Words: caudate nucleus; anxiety; neurochemical mechanisms Tranquillizers potentiating GABA-ergic transmission are known to suppress fear and deactivate the fearinduced synthesis of catecholaminergic enzymes in the caudate nucleus [4,14]. Aversive stimuli of diverse modalities converging on the caudate nucleus differently change the content of dopamine, GABA, and glutamic acid [8,10,13], or induce asymmetrical changes in their metabolism and synaptic release [11]. Although noradrenaline and serotonin also belong to neostriatal neurotransmitters [2,7,12], their role in the genesis of anxiety is unclear.In this study, the functional role of different neurotransmitters in anxiety caused by different aversive stimuli was investigated by means of local microinjections of GABA, glutamic acid, monoamines, and their agonists and antagonists into the caudate nucleus. MATERIALS AND METHODSExperiments were carried out on 42 outbred adult male rats weighing 250i70 g. The rats were tested in a box consisting of light (200-W light bulb) and dark compartments and a special section for victim rats separated from the dark compartment by a transparent wall. The light and dark compartments were connected through a hole located 6 cm above the floor. The level of anxiety was measured in rats previously trained to avoid illuminated place (test 1, illuminated platform avoidance) and to avoid light compartment in a threatening situation (test 2, threatening situation avoidance). Painful electric stimulation (45 V) applied to 18 victim rats in the special section of the dark compartment served as a model of threatening situation for spectator rats and was automatically switched off, when spectator rat reached a special platform in the dark compartment. After consolidation of the avoidance reactions, the rats (n=24) were anesthetized with ether and chemotrodes for intrastriatal microinjections were implanted in the dorsal part of the caudate nucleus according to stereotaxic coordinates AP=,I.0, L=2.0, and H=3.2. The following drugs (0.5-5%) were used: dopamine GABA, glutamic acid, serotonin creatinine sulphate, agonists of cz 2 adrenoreceptor, D 1 and D 2 dopamine receptors (clonidine, apomorphine), and antagonists of %, a2, D v and D 2 receptors (phentolamine, yohimbine, sulpiride) in doses of 5-50 ~tg. All drugs were administered in a volume of 1 ~tl. Retention of the acquired reactions was tested for 2 days before experiments (5-6 days after surgery). The rats with avoidance l...

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