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George F Koob: Influence Statistics

The purpose of this study was to test the hypothesis that activation of the dynorphin/kappa (κ)-opioid system has a role in the increased consumption of ethanol in dependent animals. The effects of three opioid receptor antagonists with different effects on opioid receptors, naltrexone, nalmefene, and nor-binaltorphimine (nor-BNI), were compared in their ability to decrease ethanol self-administration in nondependent and ethanol-dependent male Wistar rats. Nalmefene and naltrexone are ...

BACKGROUND: Gamma-aminobutyric acid-B (GABA(B)) receptor agonists have been shown to suppress operant self-administration of ethanol in nondependent rats. However, little work has focused on the effects of GABA(B) receptor agonists on self-administration of ethanol in dependent animals.

METHODS: In the present experiment, the GABA(B) receptor agonist baclofen was tested for the ability to modulate both fixed- (FR) and progressive-ratio (PR) responding for ethanol in rats while ...

Corticotropin-releasing factor (CRF) and its family of peptides are critical coordinators of homeostasis whose actions are mediated through their receptors, CRF receptor 1 (CRFR1) and CRFR2, found throughout the CNS and periphery. The phenotypes of mice deficient in either CRFR1 or CRFR2 demonstrate the critical role these receptors play. CRFR1-mutant mice have an impaired stress response and display decreased anxiety-like behavior, whereas CRFR2-mutant mice are hypersensitive to stress ...

BACKGROUND: Ethanol self-administering rats exhibit enhanced responding during withdrawal from continuous exposure to ethanol vapor. This study compared self-administration of ethanol during withdrawal from continuous versus intermittent ethanol vapor.

METHODS: Experiment 1 examined self-administration of ethanol in rats trained to self-administer ethanol after continuous, intermittent (14 hr on and 10 hr off), or no (i.e., controls) ethanol vapor exposure. Exposure time was equalized ...

Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is ...

The role of opioids, dopamine and serotonin in ethanol (EtOH) reward and preference was investigated in non-deprived, Alcohol-Preferring (P), and genetically heterogenous Wistar rats. Operant responding for ethanol was initiated using sweet-solution substitution procedures. The rats were then trained in 30-min daily sessiosn to respond for ethanol (10% v/v) versus water under a two-lever, free-choice contingency. All testing was conducted in the absence of water and food deprivation or ...

The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. Alcohol dependence is associated with increased corticotropin releasing factor (CRF) influence on CeA GABA release and CRF type 1 receptor (CRF(1)) antagonists prevent the excessive alcohol consumption associated with dependence. Genetically selected Marchigian Sardinian (msP) rats have an overactive extrahypothalamic CRF(1) system, are ...

Spontaneous locomotor activity and the locomotor response to amphetamine and apomorphine were studied in rats subjected to either radiofrequency (RF), 6-hydroxydopamine (6-OHDA) or both RF and 6-OHDA lesions of the mesolimbic dopamine (DA) system. Large 6-OHDA lesions of the ventral tegmental area (VTA) or of the nucleus accumbens (N.Acc.) produced hypo-activity in the open field, a complete blockade of the locomotor stimulating effects of D-amphetamine and a profound supersensitive ...

Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, ...

BACKGROUND: Corticotropin-releasing factor (CRF) and gamma-aminobutyric acid (GABA)ergic systems in the central amygdala (CeA) are implicated in the high-anxiety, high-drinking profile associated with ethanol dependence. Ethanol augments CeA GABA release in ethanol-naive rats and mice.

METHODS: Using naive and ethanol-dependent rats, we compared electrophysiologic effects and interactions of CRF and ethanol on CeA GABAergic transmission, and we measured GABA dialyzate in CeA after ...