Changes in anxiety in abstinence correlate with the state of the nigrostriatal system in the rat hippocampus

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Opiate dependence results from impairments of neuronal plasticity, i.e., so-called aberrant neuroplasticity, formation of which involves long-term structural-functional rearrangements persisting even during drug abstinence. Nitric oxide (NO) is involved both in mediating the effects of opiates and in the mechanisms of some types of neuroplasticity, so NO may potentially take part in the development of psychopathological processes on opiate withdrawal. The present study addressed measures of the nitrergic system (nitric oxide synthase (NOS) activity and nitrite and nitrate (NOx-) concentrations) in areas of the rat brain; anxiety was also assessed, in terms of behavioral measures in the elevated plus maze, during morphine withdrawal. NOS activity was found to increase by day 3, while the NOx- concentration was increased by day 6 of withdrawal, these changes being seen only in the hippocampus. At six days after morphine withdrawal, rats showed more entries into the open arms of the elevated plus maze and remained in these arms longer. Correlations were found between measures of the NO system in the hippocampus and the behavior of the animals in the maze. These results suggest that changes in the activity of the nitrergic system in the hippocampus represent one of the molecular mechanisms impairing the behavior of animals in abstinence.

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