Browsing by Subject "Nucleus Accumbens"

Now showing 1 - 9 of 9
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    Co-administration of ethanol and nicotine: the enduring alterations in the rewarding properties of nicotine and glutamate activity within the mesocorticolimbic system of female alcohol-preferring (P) rats
    (Springer-Verlag, 2015-12) Deehan, Gerald A.; Hauser, Sheketha R.; Waeiss, R. Aaron; Knight, Christopher P.; Toalston, Jamie E.; Truitt, William A.; McBride, William J.; Rodd, Zachary A.; Department of Psychiatry, IU School of Medicine
    RATIONALE: The co-abuse of ethanol (EtOH) and nicotine (NIC) increases the likelihood that an individual will relapse to drug use while attempting to maintain abstinence. There is limited research examining the consequences of long-term EtOH and NIC co-abuse. OBJECTIVES: The current experiments determined the enduring effects of chronic EtOH, NIC, or EtOH + NIC intake on the reinforcing properties of NIC and glutamate (GLU) activity within the mesocorticolimbic (MCL) system. METHODS: Alcohol-preferring (P) rats self-administered EtOH, Sacc + NIC, or EtOH + NIC combined for 10 weeks. The reinforcing properties of 0.1-3.0 μM NIC within the nucleus accumbens shell (AcbSh) were assessed following a 2-3-week drug-free period using intracranial self-administration (ICSA) procedures. The effects of EtOH, Sacc, Sacc + NIC, or EtOH + NIC intake on extracellular levels and clearance of glutamate (GLU) in the medial prefrontal cortex (mPFC) were also determined. RESULTS: Binge intake of EtOH (96-100 mg%) and NIC (21-27 mg/mL) were attained. All groups of P rats self-infused 3.0 μM NIC directly into the AcbSh, whereas only animals in the EtOH + NIC co-abuse group self-infused the 0.3 and 1.0 μM NIC concentrations. Additionally, self-administration of EtOH + NIC, but not EtOH, Sacc or Sacc + NIC, resulted in enduring increases in basal extracellular GLU levels in the mPFC. CONCLUSIONS: Overall, the co-abuse of EtOH + NIC produced enduring neuronal alterations within the MCL which enhanced the rewarding properties of NIC in the AcbSh and elevated extracellular GLU levels within the mPFC.
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    COMT Inhibition Alters Cue-Evoked Oscillatory Dynamics during Alcohol Drinking in the Rat
    (Society for Neuroscience, 2018-10-31) McCane, A. M.; Ahn, S.; Rubchinsky, L. L.; Janetsian-Fritz, S. S.; Linsenbardt, D. N.; Czachowski, C. L.; Lapish, C. C.; Psychology, School of Science
    Alterations in the corticostriatal system have been implicated in numerous substance use disorders, including alcohol use disorder (AUD). Adaptations in this neural system are associated with enhanced drug-seeking behaviors following exposure to cues predicting drug availability. Therefore, understanding how potential treatments alter neural activity in this system could lead to more refined and effective approaches for AUD. Local field potentials (LFPs) were acquired simultaneously in the prefrontal cortex (PFC) and nucleus accumbens (NA) of both alcohol preferring (P) and Wistar rats engaged in a Pavlovian conditioning paradigm wherein a light cue signaled the availability of ethanol (EtOH). On test days, the catechol-o-methyl-transferase (COMT) inhibitor tolcapone was administered prior to conditioning. Stimulus-evoked voltage changes were observed following the presentation of the EtOH cue in both strains and were most pronounced in the PFC of P rats. Phase analyses of LFPs in the θ band (5-11 Hz) revealed that PFC-NA synchrony was reduced in P rats relative to Wistars but was robustly increased during drinking. Presentation of the cue resulted in a larger phase reset in the PFC of P rats but not Wistars, an effect that was attenuated by tolcapone. Additionally, tolcapone reduced cued EtOH intake in P rat but not Wistars. These results suggest a link between corticostriatal synchrony and genetic risk for excessive drinking. Moreover, inhibition of COMT within these systems may result in reduced attribution of salience to reward paired stimuli via modulation of stimulus-evoked changes to cortical oscillations in genetically susceptible populations.
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    Corticostriatal and dopaminergic response to beer flavor with both fMRI and [11C]raclopride Positron Emission Tomography
    (Wiley, 2016-09) Oberlin, Brandon G.; Dzemidzic, Mario; Harezlak, Jaroslaw; Kudela, Maria A.; Tran, Stella M.; Soeurt, Christina M.; Yoder, Karmen K.; Kareken, David A.; Neurology, School of Medicine
    Background Cue-evoked drug seeking behavior likely depends on interactions between frontal activity and ventral striatal (VST) dopamine transmission. Using [11C]raclopride (RAC) positron emission tomography (PET), we previously demonstrated that beer flavor (absent intoxication) elicited VST dopamine (DA) release in beer drinkers, inferred by RAC displacement. Here, a subset of subjects from this previous RAC-PET study underwent a similar paradigm during functional magnetic resonance imaging (fMRI) to test how orbitofrontal cortex (OFC) and VST BOLD responses to beer flavor are related to VST DA release and motivation to drink. Methods Male beer drinkers (n=28, age=24±2, drinks/week=16±10) from our previous PET study participated in a similar fMRI paradigm wherein subjects tasted their most frequently consumed brand of beer and Gatorade® (appetitive control). We tested for correlations between blood oxygenation level dependent (BOLD) activation in fMRI and VST DA responses in PET, and drinking-related variables. Results Compared to Gatorade, beer flavor increased wanting and desire to drink, and induced BOLD responses in bilateral OFC and right VST. Wanting and desire to drink correlated with both right VST and medial OFC BOLD activation to beer flavor. Like the BOLD findings, beer flavor (relative to Gatorade) again induced right VST DA release in this fMRI subject subset, but there was no correlation between DA release and the magnitude of BOLD responses in frontal regions of interest. Conclusions Both imaging modalities showed a right lateralized VST response (BOLD and DA release) to a drug-paired conditioned stimulus, whereas fMRI BOLD responses in the VST and medial OFC also reflected wanting and desire to drink. The data suggest the possibility that responses to drug-paired cues may be rightward biased in the VST (at least in right-handed males), and that VST and OFC responses in this gustatory paradigm reflect stimulus wanting.
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    D1 receptors in the nucleus accumbens-shell, but not the core, are involved in mediating ethanol-seeking behavior of alcohol-preferring (P) rats
    (Elsevier, 2015-06-04) Hauser, S. R.; Deehan, G. A.; Dhaher, R.; Knight, C. P.; Wilden, J. A.; McBride, W. J.; Rodd, Z. A.; Department of Psychiatry, IU School of Medicine
    Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D1 antagonist SCH 23390 or the D1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7d ays to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1μg/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125μg/side) increased responding on the EtOH lever. Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats.
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    Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats
    (Elsevier, 2008-06) Rodd, Zachary A.; Kimpel, Mark W.; Edenberg, Howard J.; Bell, Richard L.; Strother, Wendy N.; McClintick, Jeanette N.; Carr, Lucinda G.; Liang, Tiebing; McBride, William J.; Department of Psychiatry, IU School of Medicine
    The current study examined the effects of operant ethanol (EtOH) self-administration on gene expression in the nucleus accumbens (ACB) and amygdala (AMYG) of inbred alcohol-preferring (iP) rats. Rats self-trained on a standard two-lever operant paradigm to administer either water-water, EtOH (15% v/v)-water, or saccharin (SAC; 0.0125% g/v)-water. Animals were killed 24 hr after the last operant session, and the ACB and AMYG dissected; RNA was extracted and purified for microarray analysis. For the ACB, there were 513 significant differences at the p < 0.01 level in named genes: 55 between SAC and water; 215 between EtOH and water, and 243 between EtOH and SAC. In the case of the AMYG (p < 0.01), there were 48 between SAC and water, 23 between EtOH and water, and 63 between EtOH and SAC group. Gene Ontology (GO) analysis indicated that differences in the ACB between the EtOH and SAC groups could be grouped into 15 significant (p < 0.05) categories, which included major categories such as synaptic transmission, cell and ion homeostasis, and neurogenesis, whereas differences between the EtOH and water groups had only 4 categories, which also included homeostasis and synaptic transmission. Several genes were in common between the EtOH and both the SAC and water groups in the synaptic transmission (e.g., Cav2, Nrxn, Gabrb2, Gad1, Homer1) and homeostasis (S100b, Prkca, Ftl1) categories. Overall, the results suggest that changes in gene expression in the ACB of iP rats are associated with the reinforcing effects of EtOH.
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    Elements of the Brain Network Regulating Social Behavior and Vocal Communication in Nf1+/- Mice: Relevance to Developmental Language Disorders and Autism Spectrum Disorders
    (2022-11) Karathanasis, Sotirios Ferris; Landreth, Gary E.; Clapp, D. Wade; Molosh, Andrei I.; Oblak, Adrian L.; Mosley, Amber L.; Shekhar, Anantha
    Communication is a vital tool used by humans to share information, coordinate behavior, and survive. However, the ability to communicate can become disrupted or remain absent in individuals with neurodevelopmental disorders: two prominent examples include autism spectrum disorders and developmental language disorders, found in nearly 2% and 10% of the population, respectively. Communication disorders are devastating to the autonomy and quality of life of affected individuals, but clinical solutions are limited due to the complex and often unknown neural etiology underlying these conditions. One known disorder with high incidence of disrupted communication is Neurofibromatosis type 1, the genetic disease caused by heterozygosity of the Ras GTPase-activating protein-coding gene NF1. Mice heterozygous for their ortholog of this gene (Nf1+/-) have been shown to recapitulate neuropsychiatric conditions seen in patients. Using a courtship trial paradigm as a model for testing communication, I have demonstrated that Nf1+/- male mice showed deficits in both courtship and non-courtship social behavior as well as a decrease in the number and duration of ultrasonic vocalizations (USVs). Immediate early gene (IEG) immunohistochemistry (IHC) in neurons of courtship-relevant brain regions revealed the Shell of the Nucleus Accumbens (NAcS) as a dysfunctional brain region in Nf1+/- mice compared to WT male mice following courtship trial. Optogenetic targeting of the Nucleus Accumbens (NAc) restored courtship social behaviors and USV number, but not USV duration or non-courtship gestural social behaviors, in Nf1+/- males. This study contributes to a preclinical foundation for understanding etiology of communication disorders in patients.
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    Microinjections of acetaldehyde or salsolinol into the posterior ventral tegmental area increase dopamine release in the nucleus accumbens shell
    (Wiley Blackwell (Blackwell Publishing), 2013-05) Deehan, Gerald A.; Engleman, Eric A.; Ding, Zheng-Ming; McBride, William J.; Rodd, Zachary A.; Department of Psychiatry, IU School of Medicine
    BACKGROUND: Published findings indicate that acetaldehyde (ACD; the first metabolite of ethanol [EtOH]) and salsolinol (SAL; formed through the nonenzymatic condensation of ACD and dopamine [DA]) can be formed following EtOH consumption. Both ACD and SAL exhibit reinforcing properties within the posterior ventral tegmental area (pVTA) and both exhibit an inverted "U-shaped" dose-response curve. The current study was undertaken to examine the dose-response effects of microinjections of ACD or SAL into the pVTA on DA efflux in the nucleus accumbens shell (AcbSh). METHODS: For the first experiment, separate groups of male Wistar rats received pulse microinjections of artificial cerebrospinal fluid (aCSF) or 12-, 23-, or 90-μM ACD into the pVTA, while extracellular DA levels were concurrently measured in the AcbSh. The second experiment was similarly conducted, except rats were given microinjections of aCSF or 0.03-, 0.3-, 1.0-, or 3.0-μM SAL, while extracellular levels of DA were measured in the AcbSh. RESULTS: Both ACD and SAL produced a dose-dependent inverted "U-shaped" response on DA release in the AcbSh, with 23-μM ACD (200% baseline) and 0.3-μM SAL (300% baseline) producing maximal peak responses with higher concentrations of ACD (90 μM) and SAL (3.0 μM) producing significantly lower DA efflux. CONCLUSIONS: The findings from the current study indicate that local application of intermediate concentrations of ACD and SAL stimulated DA neurons in the pVTA, whereas higher concentrations may be having secondary effects within the pVTA that inhibit DA neuronal activity. The present results parallel the studies on the reinforcing effects of ACD and SAL in the pVTA and support the idea that the reinforcing effects of ACD and SAL within the pVTA are mediated by activating DA neurons.