The Neuropharmacology of Ethanol Self-Administration

Weiss, Friedbert; Koob, George F.

doi:10.1007/978-1-4757-1305-3_7

Cited by 45 publications

(30 citation statements)

References 126 publications

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“…Low CSF HVA may have more to do with psychopathology related to alcoholism as opposed to mood disorder biology. Our finding is consistent with studies that suggest that dopaminergic mechanisms play a part in the biology of alcohol use disorders, including mechanisms of alcohol dependence and withdrawal (Diana et al, 1993;Weiss et al, 1996;Weiss and Koob, 1991;Koob, 1992;Noble, 1996;Wiesbeck et al, 2000;Fromme and D'Amico, 1999;Nevo and Hamon, 1995;Roos and Silfverskiöld, 1973;Kato et al, 1979;Goldman et al, 1992;Takahashi et al, 1974;Major et al, 1977;Fujimoto et al, 1983;Roy et al, 1991a;Virkkunen et al, 1996;Fils-Aime et al, 1996;Petrakis et al, 1999;Samson et al, 1990;Valenzuela and Harris, 1997;Robinson and Berridge, 1993;VavrousekJakuba et al, 1992;Quarfordt et al, 1991;Modell et al, 1993;Grace, 2000).…”

Section: Biological Findingssupporting

confidence: 90%

Lower CSF Homovanillic Acid Levels in Depressed Patients with a History of Alcoholism

Sher

Oquendo

et al. 2003

Neuropsychopharmacol

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Major depression and alcoholism are often comorbid, resulting in more impairment and more suicidal behavior compared with either diagnosis alone. This study compared clinical features and cerebrospinal fluid (CSF) monoamine metabolites in depressed subjects with and without a history of alcoholism and healthy volunteers. We hypothesized that depressed subjects with a history of alcoholism would be more aggressive, impulsive, and suicidal than depressed subjects without a history of alcoholism, and would have lower CSF monoamine metabolite levels. We compared 63 subjects with a current major depressive episode (MDE) and a history of alcoholism, 72 subjects with a current MDE but without a history of alcoholism, and 22 healthy volunteers. Participants with a history of alcoholism were in remission for at least 6 months. All subjects were free from prescribed medications known to affect brain serotonin, dopamine, or norepinephrine systems for a minimum of 14 days. Depressive symptoms, lifetime aggression, impulsivity, Axis II disorders, and suicidal behavior were assessed. CSF was sampled and homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were assayed by high-performance lipid chromatography with electrochemical detection. Depressed subjects with a history of alcoholism did not differ from depressed subjects without a history of alcoholism in current severity of depressive symptoms, or in past suicidal behavior. Depressed subjects with a history of alcoholism had lower CSF HVA levels, and higher lifetime aggression and current suicide ideation scale scores and were more likely to be tobacco smokers compared with depressed subjects without a history of alcoholism. Low HVA was present after adjustment for sex, aggression and depression scores, cigarette smoking, antisocial and borderline personality disorders, psychomotor retardation, and delusions. Controls had CSF HVA levels intermediate between the two depressed groups. We found no group difference in CSF 5-HIAA and MHPG levels. In individuals with current MDE, those with a history of comorbid alcoholism had lower CSF HVA levels compared with those without a history of alcoholism. Low CSF HVA suggests that impaired dopaminergic activity is associated with a history of alcoholism in persons with current MDE.

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Section: Biological Findingssupporting

confidence: 90%

Lower CSF Homovanillic Acid Levels in Depressed Patients with a History of Alcoholism

Sher

Oquendo

et al. 2003

Neuropsychopharmacol

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“…'Over, when rats were given choice between water and the polycose solution, wi out EtOJ-I. only the O.t5-mg/ kg dose supprcssc..>d wa intake during the IS-minule interval (see Figure 7A-B~ Given the reported consistency of EtOH drinking' NP rats (Mc Bride et al 1988;s', mson et al I 989b) un limited access protocols in the absence of dnlg Ire me nts, one possible interpretation of the results served in the current study during the 30-to 120-minu posld rug administr,ltion time inten'als may be that i creases in EtOH or water drinking renect elevations d to pharmacologically induced effects on Auid inta during the 1S-minute interva l (Weiss and Koob 1991 However, because the pretre<llment times with the BD ligands were all s imilar, and none of the agents w~ given after the initial hour of nuid intake, the dcgl\. 'C which eleva ted EtOH or water intake during the JO.. to 12().minute consumption inten'als represent compcns.ttory increases Cannot be dete rmined .…”

Section: Discussionmentioning

confidence: 63%

“…>d by a varie ty of neuro pharmacologica l agents that affect different neurotransmitter systems (Weiss and Koob 1991 ;McBride e t al . 1992), suggesting tha t several neurotransmitte r systems may interact to mediate EtOH reinforcement.…”

mentioning

confidence: 99%

Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats

June

Murphy

Hewitt

et al. 1996

Neuropsychopharmacology

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Bellwtiiaul'illc (8DZ) rcecIJlar ligullds willi varyingIII/ril/sic efficacies FG 7142 Ident ifying both the env ironmental and biological variables that promote and maintain high alcohol-seeking or alcohol self-administration behavior is key to unders tanding the disorder of alcohol abuse and alcoholism (Li et al. 1991). Selective breed ing methodology has demonstrated convincingly thai there is genetic int1u-ence on alcohol-seeking beh.wior ( Li et aL 1991). Currently there are four pairs (high and low) of rat lines that differ in alcohol preference (Ericksson and Rusi 1981; Mardones and Segozia-Riq uelene 1983; Li ct a l.

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“…Thus, opioid receptors within some (eg NACC and VTA), but not all mesolimbic substrates can selectively modulate EtOH-reinforced behaviors. Previous reports in the literature have suggested that a selectivity in reducing EtOH-motivated behaviors in rodents was difficult, equivocal, or not clearly observable (Brown and Holtzman, 1979;Herz, 1997;Schwartz-Stevens et al, 1992;Weiss and Koob, 1991;Weiss et al, 1990). However, we hypothesized that the operant contingencies under which one evaluates opiate receptor antagonists following parenteral or direct administrations into the CNS is a very important factor in observing selective antagonism on EtOH-motivated behaviors.…”

Section: Differential Dose and Reinforcer 'Sensitivity' Exist In The mentioning

confidence: 90%

“…While a voluminous literature support a role for nonselective and selective opioid antagonists as potential pharmacotherapies in humans, a selective role for opioid mechanisms in alcohol reward is still a matter of debate (Brown and Holtzman, 1979;Herz, 1997;Reid and Hubbell, 1992;Schwartz-Stevens et al, 1992;Weiss and Koob, 1991;Weiss et al, 1990). Some researchers have argued that while both EtOH and other palatable reinforcers are affected by opioid antagonists, the relative magnitude of suppression is far less for water, sucrose, and saccharin solutions (see June et al, 1998June et al, , 1999Heyser et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Central Opioid Receptors Differentially Regulate the Nalmefene-Induced Suppression of Ethanol- and Saccharin-Reinforced Behaviors in Alcohol-Preferring (P) Rats

June

Cummings

Eiler

et al. 2003

Neuropsychopharmacol

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The exact opioid-sensitive receptors participating in EtOH-seeking behaviors remains unclear. Previous studies have reported higher densities of m-opioid receptor binding in the nucleus accumbens (NACC) of P relative to NP rats; however, no differences were seen in d-receptor binding. In contrast to the NACC, substantially lower levels of m-receptor binding have been observed in the ventral tegmental area (VTA) of both P and NP rats, albeit no line differences have been observed. In the present study, opioid receptors in the NACC, VTA, and hippocampus were evaluated for their capacity to regulate both EtOH-and saccharin-motivated behaviors in the genetically selected alcohol-preferring (P) rat. To accomplish this, nalmefene, an opiate antagonist with preferential binding affinity for the m-opioid receptor was unilaterally or bilaterally infused during concurrent availability of 1 h daily EtOH (10% v/v) and saccharin (0.025 or 0.050% w/v) solutions. Rats performed under a two-lever fixed ratio (FR) schedule in which four responses on one lever produced the EtOH solution, and four on a second lever produced the saccharin solution. The results demonstrated that when responding maintained by both EtOH and saccharin are matched at basal levels, unilateral (1-60 mg) or bilateral (0.5-10 mg) microinjections of nalmefene into the NACC produced selective dose-dependent reductions on responding maintained by EtOH. Unilateral (40, 60 mg) and bilateral (10 mg) VTA infusions were also observed to selectively reduced EtOH responding; however, greater nalmefene doses were required and the magnitude of suppression on EtOH responding was markedly less compared with the NACC. The greater sensitivity of nalmefene to suppress EtOH responding in the NACC is likely due to the greater number of opioid receptors in the NACC relative to the VTA. Only bilateral infusion of the 40 mg dose in the NACC and VTA suppressed responding maintained by both EtOH and saccharin. In contrast, intrahippocampal infusions dose dependently suppressed EtOH-and saccharin-maintained responding over a range of doses (1-20 mg). The present study provides evidence that nalmefene suppresses EtOH-motivated behaviors via blockade of opioid receptors within the NACC and VTA, and under various dose conditions both reinforcer and neuroanatomical specificity can be observed.

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The Neuropharmacology of Ethanol Self-Administration

Cited by 45 publications

References 126 publications

Lower CSF Homovanillic Acid Levels in Depressed Patients with a History of Alcoholism

Lower CSF Homovanillic Acid Levels in Depressed Patients with a History of Alcoholism

Benzodiazepine receptor ligands with different intrinsic efficacies alter ethanol intake in alcohol-nonpreferring (NP) rats

Central Opioid Receptors Differentially Regulate the Nalmefene-Induced Suppression of Ethanol- and Saccharin-Reinforced Behaviors in Alcohol-Preferring (P) Rats

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