Accumbens neurochemical adaptations produced by binge-like alcohol consumption

Biochemical Pharmacology

Ary

Lominac

2008

Self Cite

118

160

Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

Section: Homers and Alcohol-induced Neuroplasticitymentioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Biochemical Pharmacology

Ary

Lominac

2008

Self Cite

118

160

“…The procedures for microdialysis probe construction and dialysate collection were identical to those described previously (eg Lominac et al, 2006;Szumlinski et al, 2005bSzumlinski et al, , 2007. A microdialysis probe (24 gauge, 23 mm in length, including 0.7-1.0 mm active membrane) was inserted unilaterally into the NAC and perfused at a rate of 2.0 ml/min with artificial cerebrospinal fluid.…”

Section: In Vivo Microdialysis and Hplc For Monoamines And Amino Acidsmentioning

confidence: 99%

“…For this experiment, dialysate was collected every 20 min for 1 h before, and then for 3 h following, an i.p. injection of 2 g/kg alcohol, in a manner similar to that conducted previously in Homer2 KO and B6 mice (Lominac et al, 2006;Szumlinski et al, 2005bSzumlinski et al, , 2007.…”

Section: In Vivo Microdialysis and Hplc For Monoamines And Amino Acidsmentioning

confidence: 99%

“…The high-pressure liquid chromatography (HPLC) system and the procedures for the electrochemical detection of dopamine, glutamate, and g-aminobutyric acid (GABA) in the dialysate of mice were identical to those described previously (Lominac et al, 2006;Szumlinski et al, 2007). The neurotransmitter content in each sample was analyzed by peak height and was compared with external standard curves (one for each neurotransmitter examined) for quantification using ESA Coularray for Windows software.…”

Section: In Vivo Microdialysis and Hplc For Monoamines And Amino Acidsmentioning

confidence: 99%

See 1 more Smart Citation

Accumbens Homer2 Overexpression Facilitates Alcohol-Induced Neuroplasticity in C57BL/6J Mice

Ary

Lominac

et al. 2007

Neuropsychopharmacol

178

Homer proteins are integral components of the postsynaptic density that are necessary for alcohol-induced neuroplasticity within the nucleus accumbens (NAC). In this report, we describe the effects of chronic alcohol consumption upon NAC Homer expression and investigate the functional consequences of mimicking the alcohol-induced changes in Homer expression vis-à-vis alcohol-induced changes in NAC neurochemistry and behavior. Chronic alcohol consumption under continuous access (3 months; daily intake E11.271.5 g/kg/ day) produced a robust increase in NAC Homer2 protein levels that was apparent at 2 days, 2 weeks, and 2 months following withdrawal from alcohol drinking. The increased Homer2 expression was accompanied by a less enduring elevation in total mGluR1 and NR2b levels that were evident at 2 days and 2 weeks but not at the 2-month time point. Mimicking the alcohol-induced increase in Homer2 levels by viral transfection of NAC neurons in alcohol-preferring C57BL/6J inbred mice enhanced behavioral output for alcohol reinforcement and increased alcohol intake under both preprandial and postprandial conditions. Moreover, NAC Homer2 overexpression facilitated the expression of an alcohol-conditioned place preference, as well as the development of motor tolerance. Finally, NAC Homer2 overexpression facilitated NAC glutamate and dopamine release following an acute alcohol injection and augmented alcohol-induced dopamine and glutamate sensitization, but did not affect NAC g-aminobutyric acid levels. Thus, an upregulation in NAC mGluR-Homer2-N-methyl-D-aspartic acid receptor signaling appears to be an important molecular adaptation to alcohol that promotes neuroplasticity facilitating motivational drive for alcohol and the development of alcoholism-related behaviors.

“…As described previously Szumlinski et al, 2007), the high-performance liquid chromatography (HPLC) system consisted of a Coularray detector, a Model 542 autosampler, and two Model 582 solvent-delivery systems (ESA Inc., Bedford, MA), which enabled the sequential detection of monoamines and amino acids from each dialysate sample. Dopamine and serotonin were separated using a MD-150 Â 3.2 column and detected using an ESA 5014B analytical cell with two electrodes (E1, À150 mV; E2, + 220 mV).…”

Section: Microdialysis and Hplcmentioning

confidence: 99%

Prenatal Stress Enhances Responsiveness to Cocaine

Kippin

Kapasova

et al. 2007

Neuropsychopharmacol

Early environmental events have profound influences on a wide range of adult behavior. In the current study, we assessed the influence of maternal stress during gestation on psychostimulant and neurochemical responsiveness to cocaine, cocaine self-administration, and reinstatement of cocaine-seeking in adult offspring. Pregnant, female Sprague-Dawley rats were subjected to either no treatment or to restraint stress three times per day for the last 7 days of gestation and cocaine-related behavior was assessed in offspring at 10 weeks of age. Relative to controls, a noncontingent cocaine injection elevated locomotor activity as well as nucleus accumbens levels of extracellular dopamine and glutamate to a greater extent in both cocaine-naïve and cocaine-experienced prenatal stress (PNS) rats and elevated prefrontal cortex dopamine in cocaine-experienced PNS rats. To assess the impact of PNS on cocaine addiction-related behavior, rats were trained to lever press for intravenous (i.v.) infusions of cocaine (0.25, 0.5, or 1 mg/kg/infusion), with each infusion paired with a light + tone-conditioned stimulus. Lever-pressing was extinguished and cocaine-seeking reinstated by re-exposure to the conditioned cues or by intraperitoneal cocaine-priming injections (5 or 10 mg/kg). PNS elevated active lever responding both during extinction and cocaine-primed reinstatement, but not during self-administration or conditioned-cued reinstatement. PNS also did not alter intake during self-administration. These findings demonstrate that PNS produces enduring nervous system alterations that increase the psychomotor stimulant, motivational, and neurochemical responsiveness to noncontingent cocaine. Thus, early environmental factors contribute to an individual's initial responsiveness to cocaine and propensity to relapse to cocaine-seeking.