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The selected lines of rats WHP (Warsaw High Preferring) and WLP (Warsaw Low Preferring) determine the animal model to investigate neurobiological mechanism of ethanol action. WHP rats drink excessive amounts of alcohol whereas WLP rats drink only small amounts. Patterns of ethanol consumption in WHP and WLP lines are constant. Due to cessation of alcohol intake the WHP rats have developed features of withdrawing signs. Level of dopamine and serotonine is lower in some brain regions of the WHP rats. WHP rats show an increased responsiveness to the stimulatory effects of low dose of ethanol.It has been suggested that acquisition of acute tolerance to ethanol may promote increased ethanol consumption. The effects of acute administration of ethanol (dose – 2.3 g/kg i.p.) were established by assessing ethanol-induced motor impairment, hypothermia and blood ethanol level in WHP and WLP rats. The rotarod model was used to measure motor impairment. Results have been revealed that WHP rats recovered motor activity and normal temperature when blood ethanol was at the highest level, indicating the development of acute tolerance to ethanol. The WLP rats showed similar recovery to WHP rats but at the lower blood ethanol level.Tolerance to ethanol may have a great value as a predictor of susceptibility to alcoholism therefore may signifi cant means in the relation to alcohol consumption and dependence. Generally tolerance is thought as the neuroadaptive processes to intoxicate effect of ethanol.
The aim of the study was to examine the neurochemical background of differences in the individual responses to conditioned aversive stimuli, using the strength of a rat conditioned freezing response (the contextual fear test), as a discriminating variable. It was shown that high responder (HR), i.e. rats with duration of a freezing response one standard error, or more, above the mean value, had a higher c-Fos activity in the FrA and PrL prefrontal cortical areas, and stronger 5HT immunostaining in the FrA. However, these animals had lower CRF immunostaining in the same cortical areas in comparison with low responder (LR), i.e. rats with the duration of a freezing response one standard error, or more, below the mean value. The LR group vocalized more during test session in the aversive band, and had higher serum levels of corticosterone, examined 10 min after test session. It was shown that different natural patterns of responding to conditioned aversive stimuli are associated with different expression of CRF and serotonergic- innervation of prefrontal cortical areas.
Rats were given 14 “daily” (6 doses/week) s.c. doses of 0.9% NaCl (Sal), morphine (Mor), or methadone (Met), then left untreated for 14 days, and fi nally challenged with Mor, except that half each of the Sal groups were given Sal instead. All the rats were then tested for open fi eld behavior, and were sacrifi ced 2 h post-challenge. Striatal (CPu), accumbal (Acb), sensorimotor cortex (S1) and prefrontal cortex contents of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3 MT, assessed only in the CPu and Acb) were measured by HPLC. Analysis of total distance covered by the rats showed Mor and Met-induced sensitization to Mor in the WHP rats only, whereas the distance covered in the central part of the test arena was signifi cantly affected (increased) only by the Mor pretreatment and only in the WHP rats. There was no signifi cant between-line or treatment-related difference in DA content, and no signifi cant between-line difference in baseline DA metabolite contents, except that S1 HVA content was signifi cantly higher in drug-naive WLP rats than in drug-naive WHP rats. HVA and – to a lesser extent – DOPAC contents were, in general, higher in the Mor-challenged rats than in the respective Sal-treated controls, but the differences were more pronounced in the WLP rats than in their WHP counterparts, whereas the opioid -pretreated WHP rats showed higher CPu and Acb 3 MT contents than their WLP counterparts.
In the present study, the c-Fos expression was used to map brain structures recruited during the evolution of seizures after repeated, administration of pentylenetetrazol at the subconvlusive dose (35 mg/kg, i.p.), in rats. It has been found that the earliest expression of cFos, at the stage 1,2 of kindling, appeared in the nucleus accumbensshell, the piriform cortex, the prefrontal cortex and striatum. On the 3rd stage of kindling, the central amygdala nucleus, the entorhinal cortex, and the lateral septal nucleus (LSV), showed an enhanced expression of c-Fos. On the 4th stage of kindling, c-Fos was increased in the basolateral amygdala, and CA1 area of the hippocampus. Finally, c-Fos labelling was enhanced in the dentate gyrus of the hippocampus, only when the stage 5 of kindling, i.e. the clonic-tonic convulsions, appeared. The most potent changes in c-Fos (in a descending order) were shown in the dentate gyrus, piriform cortex, CA1 area, the LSV, basolateral amygdala, central amygdala nuclei, and prefrontal cortex. It appeared, that there are important similarities in the structures recruited at the beginning and at the end of electrically and chemically-induced kindling, i.e. the piriform cortex and the hippocampal dentate gyrus, respectively. On the other hand, the differences gradually disappear at the later stages of kindling, followed by the symmetrical propagation of epileptic activity from the limbic system to the neocortex, during the generalized seizures.
In the present study the effects of a protein synthesis inhibitor, cycloheximide (125 μg, i.c.v.), on the expression and reconsolidation of pentylenetetrazol-induced kindled seizures, were studied in rats. Cycloheximide given repeatedly (every second day) to fully kindled rats, immediately after 4 consecutive sessions of PTZ-seizures, did not modify the strength of subsequent fi ts of convulsions. On the other hand, the protein synthesis inhibitor signifi cantly attenuated the strength of convulsions when the drug was administered 1 h before the PTZ injection, every second day for 5 consecutive experimental sessions. However, when cycloheximide was omitted in a consecutive session, PTZ induced a fully developed fi t of tonicclonic convulsions, indicating that cycloheximide-induced changes in seizure intensity were transitory, not related to a stable modifi cation in the function of neuronal circuits responsible for kindling seizures. The present fi ndings suggest that the mechanisms underlying epileptogenesis are very resistant to modifi cation, and as such, are not the subject to permanent changes even under the infl uence of protein synthesis inhibition. One possible reason may be the depth and multiplicity of changes induced by seizures (i.e. alterations in enzymes, receptors, structural proteins, growth factors, etc.), that may cause permanent biochemical and morphological alterations in the brain that give rise to the kindled seizures.
In recent years we have elaborated an animal model to examine the neurochemical background of differences in the individual responses to conditioned aversive stimuli, using the strength of a rat contextual fear test, as a discriminating variable: low responders (LR), i.e. rats with duration of a freezing response one standard error, or more, below the mean value and high responders (HR), i.e. rats with duration of a freezing response one standard error, or more, above the mean value. It was found that 1.5 h after a testing session of contextual fear test, the LR animals showed a higher density of 5-HT1A and glucocorticoid immunoreactivity-expressing cells (GRsir) in the cortical M2 area and hippocampal dentate gyrus as well as an increased number co-expressing 5-HT1A /GRs-ir in the same areas. The HR rats had a signifi cantly higher concentration of 5-HT1A and GRs-ir in the basolateral amygdala. The present data add more arguments for the neurobiological background of differences in individual responses to aversive conditioned stimuli.
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