ENDOGENOUS AND EXOGENOUS NEUROSTEROIDAL MODULATION OF MEMORY IN RATS WITH ALCOHOL DEPENDENCE AND AGGRESSIVE BEHAVIOR
N.O. Levicheva, A.M. Titkova, D.O. Bevzyuk, O.G. Berchenko
St “Institute of Neurology, Psychiatry and Narcology” of
National Academy of Sciences of Ukraine, Kharkiv, Ukraine
DOI: https://doi.org/10.15407/fz69.06.043
Abstract
Alcoholism and chronic stress lead to impaired cognitive
functions, which are regulated, in particular, by neurosteroid
hormones. Exogenous administration of progesterone is one
of the ways to influence the brain system of hormonal and
neurotransmitter regulation. The effect of intranasal administration of low doses of progesterone on endogenous neurosteroid modulation of working and spatial memory in male
rats with alcohol dependence and aggressive behavior was
investigated. Alcohol dependence in male rats was modeled
by voluntary intake of bread soaked in ethanol solution at a
dose of 1.2 g/kg for 30 days. Aggressiveness was determined
using the sensory contact method and the “partition” test. To
study memory processes in rats, neuroethological methods of
testing working (recognition of new objects) and spatial (orientation in the Barnes maze) memory were used. Progesterone
was administered intranasally at a dose of 80 μg per rat for
10 days. Progesterone, testosterone, and cortisol levels were
measured in the frontal neocortex (FC), hippocampus, and
serum using enzyme-linked immunosorbent assay kits. The
stimulatory effect of alcoholization on spatial memory and
impairment of working memory in male rats with aggressive
behavior was found. Zoosocial conflict on the background
of prolonged alcohol consumption leads to impaired object
recognition and spatial orientation against the background of
neurosteroid imbalance: a decrease in progesterone and testosterone content in the FC, hippocampus, serum, and an increase
in cortisol levels in these structures. Intranasal administration
of progesterone to rats with alcohol dependence and aggressive behavior offsets the negative effects of confrontational
relationships on working memory processes, restores the acquired experience to the baseline (however, the processes of
object differentiation remain weakened); leads to improved
spatial memory. The favorable effects of progesterone on
memory are accompanied by a decrease in the imbalance of
hormonal influences in brain structures with the restoration
of progesterone and testosterone concentrations in the FC,
hippocampus and serum against the background of weakening
of stress-induced glucocorticoid activity. Therefore, intranasal
administration of low doses of progesterone improves working
and spatial memory in male rats with alcohol dependence and
aggressive behavior due to the tendency to restore the balance
of hormones (progesterone, testosterone, cortisol) in the brain
structures responsible for memory.
Keywords:
working and spatial memory; neurosteroids; alcohol dependence; zoosocial conflict; intranasal progesterone administration.
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