Browsing by Subject "accumbens-tumake"

The nucleus accumbens (NAc) is located in the ventral striatum and plays a critical role in drug addiction. NAc receives dopaminergic projections from ventral tegmental area (VTA) which is activated after administration of various abused drugs. Activation of VTA increases the release of dopamine in NAc. Increased dopamine levels induce the release of acetylcholine from striatal cholinergic interneurons. These cholinergic interneurons have been related to the development of addiction and other emotion-related disorders such as depression. Previous studies have shown that a lesion of cholinergic interneurons led to an increase in morphine-induced conditioned place preference in mice. Moreover, an activation of cholinergic interneurons by designer receptors (DREADD) has reduced food consumption motivated by food restriction. The purpose of this study was to investigate whether accumbal cholinergic interneurons mediate alcohol- and morphine-induced conditioned place preference and locomotor activity. The activation of cholinergic interneurons was controlled using DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technology. DREADDs are G protein-coupled receptors. Cellular function and activation can be modulated by these receptors. DREADDs are activated by an otherwise inert synthetic ligand, clozapine-N-oxide (CNO). Fluorescent protein, mCherry, is attached to DREADDs so that the expression of receptors in brain tissue can be observed. Cre-spesific adeno-associated viruses (AAV) with DREADD gene were injected bilaterally to the nucleus accumbens of ChATcre mice in stereotactic surgery. The effects of alcohol and morphine were tested with conditioned place preference procedure. Mice were divided to three groups after DREADDs: activating receptor Gq (n = 10), inhibiting receptor Gi (n = 9) and control mC (n = 9). There were both male and female mice in every group. Alcohol did not induce conditioned place preference in any group. The locomotor activity of mice significantly increased after alcohol injection compared to saline injection. However, cholinergic interneurons had no effect on the increased locomotor activity. Morphine-induced conditioned place preference was expressed in every group but there were no significant differences between DREADDs and control group when the first 15 minutes and the whole 30 minutes of the place preference test was analysed. Though, Gq-receptor seemed to decrease the place preference compared to control group when the place preference test was observed in five minute intervals. Morphine also significantly increased the locomotor activity of mice, but there were no differences between the groups. Sex had no influence on the place preference, but female mice were more active than male mice during the alcohol conditioning and the alcohol place preference test. The locomotor activity of female mice also increased more than the activity of male mice after morphine injection. The effect of accumbal cholinergic interneurons on alcohol-induced conditioned place preference remained unclear. Activation of cholinergic interneurons suppressed morphine-induced conditioned place preference compared to control group but not enough so that the effect could be seen during the whole place preference test. The mice were same in the morphine test as in the alcohol test so the mice were conditioned to alcohol before morphine and therefore the results of morphine-induced conditioned place preference are not reliable.