PMID- 17451754
OWN - NLM
STAT- MEDLINE
DCOM- 20071025
LR  - 20181113
IS  - 0028-3908 (Print)
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 52
IP  - 8
DP  - 2007 Jun
TI  - Blockade of GABA(A) receptors within the extended amygdala attenuates D(2) 
      regulation of alcohol-motivated behaviors in the ventral tegmental area of 
      alcohol-preferring (P) rats.
PG  - 1570-9
AB  - The dopamine (DA) mesolimbic pathway, which originates from DA cell bodies within 
      the ventral tegmental area (VTA), has been shown by various studies to play a 
      role in the mediation of various drugs of abuse including alcohol (EtOH). It has 
      been suggested that the VTA's control of EtOH reward is mediated in part by the 
      D2 receptors within the VTA. These receptors may be under the regulation of 
      reciprocal GABAergic inputs from forebrain components of the mesolimbic path such 
      as the nucleus accumbens (NAcc), a classic EtOH reward substrate, and the bed 
      nucleus of the stria terminalis, a substrate recently implicated in EtOH 
      reinforcement, forming a self-regulating feedback loop. To test this hypothesis, 
      D2 regulation of EtOH self-administration (SA) was evaluated by the microinfusion 
      of the D2 antagonist eticlopride into the VTA of P rats, which produced profound 
      reductions in EtOH SA in the highest (20.0 and 40.0microg) doses tested in both 
      BST/VTA and NAcc/VTA implanted P rats. To determine the role of GABA in the 
      mediation of EtOH SA, a 32.0ng dose the non-selective GABA antagonist SR 95531 
      was microinfused into the BST producing no effect on responding for EtOH and into 
      the NAcc which lead to a reduction in EtOH responding. Finally, the hypothesis 
      that GABA innervation of the VTA from the mesolimbic forebrain may influence EtOH 
      SA was examined by the simultaneous infusion of eticlopride (40.0microg) into the 
      VTA and SR 95531 (32.0ng) into either the BST or NAcc. This combination infusion 
      completely attenuated the reduction in EtOH SA observed with the 40.0microg dose 
      of eticlopride alone in both groups of animals. These results suggest that while 
      the D2 receptors within the VTA regulate EtOH-motivated behaviors, this is 
      modulated by GABAergic input from the mesolimbic forebrain, specifically from the 
      BST and NAcc.
FAU - Eiler, William J A 2nd
AU  - Eiler WJ 2nd
AD  - Psychobiology of Addictions Program, Department of Psychology, Indiana 
      University-Purdue University, Indianapolis, IN 46202, USA.
FAU - June, Harry L
AU  - June HL
LA  - eng
GR  - R37 AA010422/AA/NIAAA NIH HHS/United States
GR  - AA10406/AA/NIAAA NIH HHS/United States
GR  - R01 AA012407-05/AA/NIAAA NIH HHS/United States
GR  - P01 GM047818/GM/NIGMS NIH HHS/United States
GR  - R01 AA012407/AA/NIAAA NIH HHS/United States
GR  - R01 AA010422/AA/NIAAA NIH HHS/United States
GR  - AA11555/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070312
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Central Nervous System Depressants)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Drug Combinations)
RN  - 0 (GABA Antagonists)
RN  - 0 (Pyridazines)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, GABA-A)
RN  - 0 (Salicylamides)
RN  - 3K9958V90M (Ethanol)
RN  - 99460MG420 (gabazine)
RN  - J8M468HBH4 (eticlopride)
SB  - IM
MH  - Amygdala/drug effects/*physiology
MH  - Animals
MH  - Behavior, Addictive/*metabolism
MH  - Behavior, Animal
MH  - Central Nervous System Depressants/administration & dosage
MH  - Conditioning, Operant/drug effects/*physiology
MH  - Dopamine Antagonists/administration & dosage
MH  - Dose-Response Relationship, Drug
MH  - Drug Combinations
MH  - Ethanol/administration & dosage
MH  - Female
MH  - GABA Antagonists/pharmacology
MH  - Male
MH  - Pyridazines/pharmacology
MH  - Rats
MH  - Receptors, Dopamine D2/*metabolism
MH  - Receptors, GABA-A/*metabolism
MH  - Salicylamides/administration & dosage
MH  - Ventral Tegmental Area/drug effects/*physiology
PMC - PMC2743737
MID - NIHMS26150
EDAT- 2007/04/25 09:00
MHDA- 2007/10/27 09:00
PMCR- 2009/09/14
CRDT- 2007/04/25 09:00
PHST- 2006/05/09 00:00 [received]
PHST- 2007/02/27 00:00 [revised]
PHST- 2007/03/01 00:00 [accepted]
PHST- 2007/04/25 09:00 [pubmed]
PHST- 2007/10/27 09:00 [medline]
PHST- 2007/04/25 09:00 [entrez]
PHST- 2009/09/14 00:00 [pmc-release]
AID - S0028-3908(07)00056-1 [pii]
AID - 10.1016/j.neuropharm.2007.03.001 [doi]
PST - ppublish
SO  - Neuropharmacology. 2007 Jun;52(8):1570-9. doi: 10.1016/j.neuropharm.2007.03.001. 
      Epub 2007 Mar 12.