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We seek to identify the molecular basis of severe psychiatric conditions in order to improve the quality of life for affected individuals. We are primarily interested in ameliorating those processes that allow for deleterious motivations and choices to impact societal and familial interactions. Specifically, these phenomena are studied in models of alcoholism, cocaine addiction, and methamphetamine addiction. Additionally, our findings are being developed into diagonistic tools.
Alcohol abuse continues to extract significant economic and societal resources. This is due, in part, to an increase in the motivation to seek alcohol that develops over time. This heightened motivation to seek alcohol often continues to manifest as chronic recidivism during abstinence. Few pharmacotherapies are available to the clinician and those that are available present either with low compliance or low efficacy. Development of more robust treatment regimens is hampered by pre-clinical models of alcoholism that often fail rigorous validity criteria and/or do not yield desired levels of pharmacological intoxication. Thus, our efforts are divided into two major, yet related tracks.
First, we seek to develop simple and efficient models of alcoholism with which specific aspects of alcoholism can be probed at the molecular level. Second, we seek to understand the molecular mechanisms through which the etiology of pathological alcohol-seeking develops and is expressed as relapse. Thus, our overall goal is to identify novel regulators of this heightened motivation to seek alcohol and, further, to ameliorate alcoholism by specifically targeting these mechanisms. To date, our efforts along with our collaborators have identified the Activators of G-protein Signaling 3/ G-protein Signaling Modulator 1 and the Small Conductance, Calcium-Activated Potassium Channel, 3rd Subunit as highly promising candidates warranting further investigation.
The psychostimulants (cocaine and crystal meth) rewire brain circuitry and reshape cell populations as well as their molecular make up. Many of these changes are long-lasting even into protracted periods of abstinence. These long-lasting changes are hypothesized to interfere with abstinence efforts. Our goal is to determine if and how these alterations contribute to addiction and relapse. Specifically, we are most interested in determining the molecular basis of the motivation and choice to seek psychostimulants despite mounting deleterious consequences. Importantly, we use this information to design novel interventions that could be efficacious in future clinical interventions.
Sanjakdar SS; Maldoon PP; Marks MJ; Brunzell DH; Maskos U; McIntosh JM; Bowers MS; Damaj MI, 2015. Differential roles of α6β2* and α4β2* neuronal nicotinic receptors in nicotine- and cocaine-conditioned reward in mice.  Neuropsychopharmacology 40(2):350-60
Bull C; Syed WA; Minter SC; Bowers MS, 2015. Differential response of glial fibrillary acidic protein-positive astrocytes in the rat prefrontal cortex following ethanol self-administration.  Alcohol Clin Exp Res 39(4):650-8
Poland RS; Bull C; Syed WA; Bowers MS, 2015. Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior.  J Vis Exp.
Leitl MD; Onvani S; Bowers MS; Cheng K; Rice KC; Carlezon WA Jr; Banks ML; Negus SS, 2014. Pain-related depression of the mesolimbic dopamine system in rats: expression, blockade by analgesics, and role of endogenous κ-opioids.  Neuropsychopharmacology 39(3):614-24
Bull C; Freitas KC; Zou S; Poland RS; Syed WA; Urban DJ; Minter SC; Shelton KL; Hauser KF; Negus SS; Knapp PE; Bowers MS, 2014. Rat nucleus accumbens core astrocytes modulate reward and the motivation to self-administer ethanol after abstinence.  Neuropsychopharmacology 39(12):2835-45
Fitting S; Knapp PE; Zou S; Marks WD; Bowers MS; Akbarali HI; Hauser KF, 2014. Interactive HIV-1 Tat and morphine-induced synaptodendritic injury is triggered through focal disruptions in Na⁺ influx, mitochondrial instability, and Ca²⁺ overload.  J Neurosci 34(38):12850-64
Cui M; Qin G; Yu K; Bowers MS; Zhang M, 2014. Targeting the Small- and Intermediate-Conductance Ca-Activated Potassium Channels: The Drug-Binding Pocket at the Channel/Calmodulin Interface.  Neurosignals 22(2):65-78
Alajaji M; Bowers MS; Knackstedt L; Damaj MI, 2013. Effects of the beta-lactam antibiotic ceftriaxone on nicotine withdrawal and nicotine-induced reinstatement of preference in mice.  Psychopharmacology (Berl) 228(3):419-26
Fuller BF; Cortes DF; Landis MK; Yohannes H; Griffin HE; Stafflinger JE; Bowers MS; Lewis MH; Fox MA; Ottens AK, 2012. Exposure of rats to environmental tobacco smoke during cerebellar development alters behavior and perturbs mitochondrial energetics.  Environ Health Perspect 120(12):1684-91
Janak PH; Bowers MS; Corbit LH, 2012. Compound stimulus presentation and the norepinephrine reuptake inhibitor atomoxetine enhance long-term extinction of cocaine-seeking behavior.  Neuropsychopharmacology 37(4):975-85
Hopf FW; Chang SJ; Sparta DR; Bowers MS; Bonci A, 2010. Motivation for alcohol becomes resistant to quinine adulteration after 3 to 4 months of intermittent alcohol self-administration.  Alcohol Clin Exp Res 34(9):1565-73
Hopf FW; Bowers MS; Chang SJ; Chen BT; Martin M; Seif T; Cho SL; Tye K; Bonci A, 2010. Reduced nucleus accumbens SK channel activity enhances alcohol seeking during abstinence.  Neuron 65(5):682-94
Bowers MS, 2010. Activators of G-protein signaling 3: a drug addiction molecular gateway.  Behav Pharmacol 21(5-6):500-13
Bowers MS; Chen BT; Bonci A, 2010. AMPA receptor synaptic plasticity induced by psychostimulants: the past, present, and therapeutic future.  Neuron 67(1):11-24
Speca DJ; Chihara D; Ashique AM; Bowers MS; Pierce-Shimomura JT; Lee J; Rabbee N; Speed TP; Gularte RJ; Chitwood J; Medrano JF; Liao M; Sonner JM; Eger EI 2nd; Peterson AS; McIntire SL, 2010. Conserved role of unc-79 in ethanol responses in lightweight mutant mice.  PLoS Genet 6.
Wanat MJ; Sparta DR; Hopf FW; Bowers MS; Melis M; Bonci A, 2009. Strain specific synaptic modifications on ventral tegmental area dopamine neurons after ethanol exposure.  Biol Psychiatry 65(8):646-53
Borgland SL; Chang SJ; Bowers MS; Thompson JL; Vittoz N; Floresco SB; Chou J; Chen BT; Bonci A, 2009. Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers.  J Neurosci 29(36):11215-25
Stuber GD; Klanker M; de Ridder B; Bowers MS; Joosten RN; Feenstra MG; Bonci A, 2008. Reward-predictive cues enhance excitatory synaptic strength onto midbrain dopamine neurons.  Science 321(5896):1690-2
Chen BT; Bowers MS; Martin M; Hopf FW; Guillory AM; Carelli RM; Chou JK; Bonci A, 2008. Cocaine but not natural reward self-administration nor passive cocaine infusion produces persistent LTP in the VTA.  Neuron 59(2):288-97
Bowers MS; Hopf FW; Chou JK; Guillory AM; Chang SJ; Janak PH; Bonci A; Diamond I, 2008. Nucleus accumbens AGS3 expression drives ethanol seeking through G betagamma.  Proc Natl Acad Sci U S A 105(34):12533-8
Szumlinski KK; Diab ME; Friedman R; Henze LM; Lominac KD; Bowers MS, 2007. Accumbens neurochemical adaptations produced by binge-like alcohol consumption.  Psychopharmacology (Berl) 190(4):415-31
Bowers MS; Chen BT; Chou JK; Osborne MP; Gass JT; See RE; Bonci A; Janak PH; Olive MF, 2007. Acamprosate attenuates cocaine- and cue-induced reinstatement of cocaine-seeking behavior in rats.  Psychopharmacology (Berl) 195(3):397-406
Hopf FW; Martin M; Chen BT; Bowers MS; Mohamedi MM; Bonci A, 2007. Withdrawal from intermittent ethanol exposure increases probability of burst firing in VTA neurons in vitro.  J Neurophysiol 98(4):2297-310
Martin M; Chen BT; Hopf FW; Bowers MS; Bonci A, 2006. Cocaine self-administration selectively abolishes LTD in the core of the nucleus accumbens.  Nat Neurosci 9(7):868-9
Kennedy AW; Gruber JB; Bolton PR; Bowers MS, 2005. Modeling gain-medium diffraction in super-Gaussian coupled unstable laser cavities.  Appl Opt 44(7):1283-7
Bowers MS; McFarland K; Lake RW; Peterson YK; Lapish CC; Gregory ML; Lanier SM; Kalivas PW, 2004. Activator of G protein signaling 3: a gatekeeper of cocaine sensitization and drug seeking.  Neuron 42(2):269-81
Bowers MS; Kalivas PW, 2003. Forebrain astroglial plasticity is induced following withdrawal from repeated cocaine administration.  Eur J Neurosci 17(6):1273-8
Kalivas PW; Toda S; Bowers MS; Baker DA; Ghasemzadeh MB, 2003. The temporal sequence of changes in gene expression by drugs of abuse.  Methods Mol Med 79:3-11
Gerstenberger DC; Trautmann TM; Bowers MS, 2003. Noncritically phase-matched second-harmonic generation in cesium lithium borate.  Opt Lett 28(14):1242-4
Bowers MS; Lake RW; McFarland K; Peterson YK; Lanier SM; Lapish CC; Kalivas PW, 2003. AGS3: a G-Protein regulator of addiction-associated behaviors.  Ann N Y Acad Sci 1003:356-7
Bowers MS; Lake RW; Rubinchik S; Dong JY; Kalivas PW, 2003. Elucidation of Homer 1a function in the nucleus accumbens using adenovirus gene transfer technology.  Ann N Y Acad Sci 1003:419-21
Mackler SA; Korutla L; Cha XY; Koebbe MJ; Fournier KM; Bowers MS; Kalivas PW, 2000. NAC-1 is a brain POZ/BTB protein that can prevent cocaine-induced sensitization in the rat.  J Neurosci 20(16):6210-7