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GABA(A) receptors containing (alpha)5 subunits in the CA1 and CA3 hippocampal fields regulate ethanol-motivated behaviors: an extended ethanol reward circuitry.
June HL, Harvey SC, Foster KL, McKay PF, Cummings R, Garcia M, Mason D, Grey C, McCane S, Williams LS, Johnson TB, He X, Rock S, Cook JM.
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GABA receptors within the mesolimbic circuitry have been proposed to play a role in regulating alcohol-seeking behaviors in the alcohol-preferring (P) rat. However, the precise GABA(A) receptor subunit(s) mediating the reinforcing properties of EtOH remains unknown. We examined the capacity of intrahippocampal infusions of an alpha5 subunit-selective ( approximately 75-fold) benzodiazepine (BDZ) inverse agonist [i.e., RY 023 (RY) (tert-butyl 8-(trimethylsilyl) acetylene-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5a] [1,4] benzodiazepine-3-carboxylate)] to alter lever pressing maintained by concurrent presentation of EtOH (10% v/v) and a saccharin solution (0.05% w/v). Bilateral (1.5-20 microgram) and unilateral (0.01-40 microgram) RY dose-dependently reduced EtOH-maintained responding, with saccharin-maintained responding being reduced only with the highest doses (e.g., 20 and 40 microgram). The competitive BDZ antagonist ZK 93426 (ZK) (7 microgram) reversed the RY-induced suppression on EtOH-maintained responding, confirming that the effect was mediated via the BDZ site on the GABA(A) receptor complex. Intrahippocampal modulation of the EtOH-maintained responding was site-specific; no antagonism by RY after intra-accumbens [nucleus accumbens (NACC)] and intraventral tegmental [ventral tegmental area (VTA)] infusions was observed. Because the VTA and NACC contain very high densities of alpha1 and alpha2 subunits, respectively, we determined whether RY exhibited a "negative" or "neutral" pharmacological profile at recombinant alpha1beta3gamma2, alpha2beta3gamma2, and alpha5beta3gamma2 receptors expressed in Xenopus oocytes. RY produced "classic" inverse agonism at all alpha receptor subtypes; thus, a neutral efficacy was not sufficient to explain the failure of RY to alter EtOH responding in the NACC or VTA. The results provide the first demonstration that the alpha5-containing GABA(A) receptors in the hippocampus play an important role in regulating EtOH-seeking behaviors.
Bradberry,
The anxiogenic beta-carboline FG 7142 selectively increases dopamine release in rat prefrontal cortex as measured by microdialysis.
1991, Pubmed
Bradberry,
The anxiogenic beta-carboline FG 7142 selectively increases dopamine release in rat prefrontal cortex as measured by microdialysis.
1991,
Pubmed Carroll,
A concurrently available nondrug reinforcer prevents the acquisition or decreases the maintenance of cocaine-reinforced behavior.
1989,
Pubmed Charlton,
Chronic ethanol administration regulates the expression of GABAA receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus.
1997,
Pubmed Crestani,
Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues.
1999,
Pubmed Duka,
Human studies on the benzodiazepine receptor antagonist beta-carboline ZK 93,426: preliminary observations on psychotropic activity.
1987,
Pubmed Duncan,
Distribution of [3H]zolpidem binding sites in relation to messenger RNA encoding the alpha 1, beta 2 and gamma 2 subunits of GABAA receptors in rat brain.
1995,
Pubmed Fritschy,
GABAA-receptor heterogeneity in the adult rat brain: differential regional and cellular distribution of seven major subunits.
1995,
Pubmed Giorgi,
Ro 15-4513, like anxiogenic beta-carbolines, increases dopamine metabolism in the prefrontal cortex of the rat.
1988,
Pubmed Graham,
Pharmacological profile of benzodiazepine site ligands with recombinant GABAA receptor subtypes.
1996,
Pubmed Groenewegen,
Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin.
1987,
Pubmed Gu,
Synthesis and evaluation of imidazo[1,5-a][1,4]benzodiazepine esters with high affinities and selectivities at "diazepam-insensitive" benzodiazepine receptors.
1993,
Pubmed Haefely,
Pharmacology of benzodiazepine antagonists.
1985,
Pubmed Harvey,
Determinants of specificity for alpha-conotoxin MII on alpha3beta2 neuronal nicotinic receptors.
1997,
Pubmed
,
Xenbase Hodge,
GABAergic transmission in the nucleus accumbens is involved in the termination of ethanol self-administration in rats.
1995,
Pubmed Izquierdo,
GABAA receptor modulation of memory: the role of endogenous benzodiazepines.
1991,
Pubmed Jensen,
Evaluation of the beta-carboline ZK 93 426 as a benzodiazepine receptor antagonist.
1984,
Pubmed June,
The novel benzodiazepine inverse agonist RO19-4603 antagonizes ethanol motivated behaviors: neuropharmacological studies.
1998,
Pubmed June,
The opioid receptor antagonist nalmefene reduces responding maintained by ethanol presentation: preclinical studies in ethanol-preferring and outbred Wistar rats.
1998,
Pubmed June,
High-affinity benzodiazepine antagonists reduce responding maintained by ethanol presentation in ethanol-preferring rats.
1998,
Pubmed June,
Ethanol self-administration in freely feeding and drinking rats: effects of Ro15-4513 alone, and in combination with Ro15-1788 (flumazenil).
1994,
Pubmed June,
GABAA-benzodiazepine receptors in the striatum are involved in the sedation produced by a moderate, but not an intoxicating ethanol dose in outbred Wistar rats.
1998,
Pubmed
,
Xenbase June,
The effects of the novel benzodiazepine receptor inverse agonist Ru 34000 on ethanol-maintained behaviors.
1998,
Pubmed June,
Effects of the benzodiazepine inverse agonist RO19-4603 alone and in combination with the benzodiazepine receptor antagonists flumazenil, ZK 93426 and CGS 8216, on ethanol intake in alcohol-preferring (P) rats.
1996,
Pubmed June,
The delta 2-opioid receptor antagonist naltriben reduces motivated responding for ethanol.
1999,
Pubmed June,
Benzodiazepine receptor antagonists modulate the actions of ethanol in alcohol-preferring and -nonpreferring rats.
1998,
Pubmed Kelley,
The distribution of the projection from the hippocampal formation to the nucleus accumbens in the rat: an anterograde- and retrograde-horseradish peroxidase study.
1982,
Pubmed Koob,
Cellular and molecular mechanisms of drug dependence.
1988,
Pubmed Koob,
The role of the striatopallidal and extended amygdala systems in drug addiction.
1999,
Pubmed Koob,
Neurocircuitry targets in ethanol reward and dependence.
1998,
Pubmed Liu,
Synthesis and pharmacological properties of novel 8-substituted imidazobenzodiazepines: high-affinity, selective probes for alpha 5-containing GABAA receptors.
1996,
Pubmed
,
Xenbase McBride,
Animal models of alcoholism: neurobiology of high alcohol-drinking behavior in rodents.
1998,
Pubmed McCullough,
Anxiogenic drugs beta-CCE and FG 7142 increase extracellular dopamine levels in nucleus accumbens.
1992,
Pubmed McKinzie,
Effects of taste aversion training on the acquisition of alcohol drinking in adolescent P and HAD rat lines.
1996,
Pubmed McNaughton,
A gene promotes anxiety in mice-and also in scientists.
1999,
Pubmed Nowak,
Blocking GABA(A) receptors in the anterior ventral tegmental area attenuates ethanol intake of the alcohol-preferring P rat.
1998,
Pubmed Phillips,
Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning.
1992,
Pubmed Pritchett,
Type I and type II GABAA-benzodiazepine receptors produced in transfected cells.
1989,
Pubmed Puia,
Influence of recombinant gamma-aminobutyric acid-A receptor subunit composition on the action of allosteric modulators of gamma-aminobutyric acid-gated Cl- currents.
1991,
Pubmed Rassnick,
GABA antagonist and benzodiazepine partial inverse agonist reduce motivated responding for ethanol.
1993,
Pubmed Rodefer,
Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys.
1999,
Pubmed Scheel-Krüger,
Dopamine-GABA interactions: evidence that GABA transmits, modulates and mediates dopaminergic functions in the basal ganglia and the limbic system.
1986,
Pubmed Skolnick,
[3H]RY 80: A high-affinity, selective ligand for gamma-aminobutyric acidA receptors containing alpha-5 subunits.
1997,
Pubmed Sur,
Autoradiographic localization of alpha5 subunit-containing GABAA receptors in rat brain.
1999,
Pubmed Suzdak,
A selective imidazobenzodiazepine antagonist of ethanol in the rat.
1986,
Pubmed Turner,
Immunohistochemical mapping of gamma-aminobutyric acid type-A receptor alpha subunits in rat central nervous system.
1993,
Pubmed von Blankenfeld,
Differential benzodiazepine pharmacology of mammalian recombinant GABAA receptors.
1990,
Pubmed Wafford,
Functional comparison of the role of gamma subunits in recombinant human gamma-aminobutyric acidA/benzodiazepine receptors.
1993,
Pubmed
,
Xenbase Wisden,
The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon.
1992,
Pubmed Wong,
High affinity ligands for 'diazepam-insensitive' benzodiazepine receptors.
1992,
Pubmed
