Monoaminergic effects of the unilateral blockade of orexin receptors (OX1R) in the enlarged amygdala under psychostimulant action

Abstract

BACKGROUND: The search for new drugs potentially effective in stopping the development of pathological addictions is an urgent task of experimental psychopharmacology.

AIM: To examine the participation of brain monoaminergic systems in the mechanisms of the blocking effect of SB-408124 on the self-stimulation of the lateral hypothalamus activated with the psychostimulant β-phenylisopropylamine (PIPA) treatment.

MATERIALS AND METHODS: Male Wistar rats pre-administered with psychostimulant (PIPA, 1 mg/kg intraperitoneally) were unilaterally injected with an orexin antagonist SB-408124 (1 μg in 1 μL) into the central nucleus of the amygdala or the bed nucleus of the stria terminalis (BNST). High-performance liquid chromatography with electrochemical detection was used to determine the levels of monoamines and their metabolites: norepinephrine (NA), dopamine (DA), serotonin (5-HT), dioxyphenylacetic (DOPAC), homovaniline (HVA), and 5-hydroxyindolacetic (5-HIAA) acids on the left and right sides of the prefrontal cortex, hippocampus, striatum, and olfactory tubercle.

RESULTS: Under the action of PIPA, microinjections of SB-408124 into the right central nucleus of the amygdala induced the following effects: prefrontal cortex, an increase in the levels of HVA and 5-HT on the right side and 5-HIAA on the left; hippocampus, bilateral increase in the levels of NA and HVA and 5-HT on the right; striatum, bilateral increase in the level of DA and the left-sided increase in HVA, 5-HT, and 5-HIAA. Microinjections into the left central nucleus of the amygdala caused a right-sided decrease in NA levels, an increase in 5-HT levels, and a left-sided decrease in DA and DOPAC levels in the striatum and a left-sided increase in HVA level in the olfactory tubercle. Microinjections into the right BNST caused a left-sided decrease in the levels of NA and DA in the prefrontal cortex, bilateral decrease in DOPAC levels, a right-sided increase in 5-HT levels, and a left-sided increase in 5-HIAA levels in the striatum; and a left-sided increase in HVA levels in the olfactory tubercle. Microinjections into the left BNST caused increased 5-HT levels in the left striatum and decreased DOPAC and 5-HIAA levels in the left olfactory tubercle.

CONCLUSIONS: Right-sided microinjections cause a greater number of changes in monoamine metabolism than left-sided ones. The introduction of SB-408124 into the right structures of the enlarged amygdala increases 5-HIAA levels in the left striatum, whereas microinjections in BNST lead to increased 5-HT levels in the ipsilateral striatum and in the contralateral in the central nucleus of the amygdala

Keywords

BNST / brain asymmetry / central amygdala nucleus / monoamines / orexin antagonist

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