Browsing by Subject "ventral pallidum"

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  • Ylitalo, Merja (Helsingfors universitet, 2016)
    Ethanol intake and the use of several drugs of abuse lead to the activation of the endogenous opioid system which has an important role in reward and reinforcement. Ethanol can affect also many other neurotransmitter systems, for example the dopaminergic, GABAergic and glutamatergic systems. The ability of opioid antagonists to decrease ethanol intake refers to the important role of the opioidergic system in mediating the reinforcement from ethanol. Important brain areas in the mesolimbic reward system are the ventral tegmental area, nucleus accumbens and ventral pallidum. The ventral pallidum is regarded as the endpoint of the mesolimbic reward system and as the cross point of the motivational circuit and reward circuit. The role of the ventral pallidum and its GABAergic and opioidergic systems in ethanol reinforcement has been proven in many studies. This review goes through the brain areas involved in the reward circuit and ethanol's effects on the neurotransmitter systems connected to the reward system. This review concentrates especially on the opioidergic system and on the role of the ventral pallidum in ethanol reinforcement. The aim of this study was to research the role µ-opioid receptors in the ventral pallidum on ethanol intake using an ethanol-preferring AA (Alko, Alcohol) rat line. The hypothesis of the study was that local inhibition of the ventral pallidum with an excess of µ-opioid receptors effects ethanol intake. We infused µ-opioid receptor gene overexpressing viral vectors (AAV-MOR), control vectors or vehicle into the ventral pallidum of rats. Ethanol drinking of the rats was examined in the limited access paradigm. After the ethanol drinking study rats received injections of an opioid receptor antagonist, naltrexone (0.1 mg/kg and 0.3 mg/kg, s.c) and an opioid receptor agonist, morphine (3 mg/kg, repeatedly, s.c) before the ethanol drinking session to see what effect the drugs have on ethanol drinking. The biological activity of the viral vectors was confirmed with immunohistochemical staining and qPCR. In the ethanol drinking study there were no statistically significant differences between the groups. Naltrexone 0.1 mg/kg dose decreased statistically significantly ethanol drinking only in AAV-MOR group and caused statistically significant difference in ethanol drinking between the AAV-MOR and control vector groups when proportionate to the control. These results suggest that possibly part of to that naltrexone's ethanol intake decreasing effects are mediated via the ventral pallidum. Morphine did not cause statistically significant differences in ethanol drinking between the groups. The results of this study do not exclude the role of the ventral pallidum in controlling ethanol drinking.
  • Suo-Yrjö, Ville (Helsingfors universitet, 2010)
    Nearly all drugs that are abused release dopamine in the nucleus accumbens, the end point structure of mesolimbic dopamine pathway. This why effect of those drugs is closely attached to dopaminergic system. It seems that function of mesolimbic dopamine pathway is necessary for rewarding effects of drugs as cocaine and amphetamine. However rewarding effects of ethanol seems to mediate routes despite of mesolimbic dopamine pathway. This conclusion is a result of several studies that have showed that destruction of synapses of in nucleus accumbens have no effect on ethanol drinking of rats. So it might be that the possible place were effects of ethanol mediate beside of straight stimulation of nucleus accumbens, are GABA- and opioidergic medium spiny neurons that project from nucleus accumbens to ventral pallidum and also from ventral pallidum back to nucleus accumbens. Ventral pallidum is the structure of brain that is thought to be the last common pathway of brain reward circuitry. Ventral pallidum is also found to mediate reinforcement of pleasure of natural rewarders and also drugs that are abused. Meaning of this study was to find how opioidreceptors in ventral pallidum control the drinking of ethanol. The method of study was observe how opioidergic drugs (µ-, δ-, κ-agonist and -antagonist) that are microinjected in brain of AA-rats mediate voluntary ethanol drinking of these animals. Hypothesis of this study was that activation of opioidreceptors in ventral pallidum leads to lower consumption of ethanol and inactivation of these receptors leads to higher consumption of ethanol. Study was performed in National institute for health and welfare, Department of Alcohol, Drugs an Addiction, in research group of Kalervo Kiianmaa. There were used ethanol prefering AA-rats which were microinjected in ventral pallidum with opioidergic drugs. Study involved 72 male rats form generation F99. There were six groups and each had 12 rats. Before the actual trial rats were taught to drink 10 % ethanol/water-solution voluntary. Surgery and placement of canulaes were done with stereotactic device. Bilateral guide canulaes were placed above the ventral pallidum. Each drug was given in three different size doses and also ringer's solution was given as a control. Volume on injections were in each drug and with the ringer's solution 0,3 µl and rate of injection was 0,3 µl/min. Total trial involved four experiment days (three with the drugs and one with the ringer's solution). Injections were given in mixed order. Immediately after injection rats were moved in their homecages and they were given drinking bottle which was filled with ethanol. The consumption of ethanol was observed in time of 10, 20, 30, 50, 70 and 90 minutes. After all experiment's were done rats were decapitated and the places of injections were checked from brain slices that were stained with thionine. Results were analyzed with repeated measures ANOVA and if difference between groups were found the post hoc test were done with Dunnett's test. If the statistical difference were found with repeated measures ANOVA the result were analyzed also in exact time point with ANOVA and Dunnett's test. The only significant result was found with µ-opioidreceptoragonist (DAMGO). It lowered the ethanol consumption significantly. The drop in ethanol consumption was dose dependent and was seen with two highest doses of DAMGO. Clearest difference was seen at the first 50 minutes after rats had started drinking ethanol. The second highest dose of µ-opioidreceptorantagonist (CTOP) had a little tendency to elevate ethanol consumption and was near to be a significant (p=0.08). There were found no effects with other drugs. The main conclusion of this study was that activation of µ-opioidreceptors in the ventral pallidum lowers consumption of ethanol in AA-rats. Inhibition the µ-opioidreceptors had a mild effect of elevating ethanol consumption but this could not be taken as reliable and more studies are needed to be done. δ- and κ-opioidreceptor activation or inhibition had no effect in ethanol consumption in these rats. Conclusions made by these results give support to the theory of role of ventral pallidum as a part of brain reward circuitry. When these results are compared to studies were GABAergic drugs are injected in ventral pallidum and ethanol consumption is observed and also with the knowledge of how these drugs affect the cell's membrane potential, there can be made conclusion that inhibition the activity of ventral pallidum has effects that block pleasure mechanisms that interface with ethanol.