Glutamate and dopamine synaptic terminals in extended amygdala after 14-week chronic alcohol drinking in inbred alcohol-preferring rats.
Alcohol has been shown to affect glutamate (GLU) and dopamine (DA) release and their correlated receptors in the key reward center--extended amygdala--which includes the shell of nucleus accumbens (sNAc) and central nucleus of amygdala (cAmg). It is unclear to date whether there is an alteration in the number of presynaptic GLU/DA nerve terminals. In this study, we investigated the number of GLU and DA terminals in the extended amygdala of alcohol-preferring (P) rats that chronically drank ethanol. P rats have a propensity to drink ethanol to intoxication and develop an alcohol dependency. The P rats were divided into (1) Water group given ad libitum chow and water for 14 weeks; (2) Continuous alcohol group (C-Alc) given ad libitum chow and choice of 15 or 30% (v/v) ethanol or water for 14 weeks; and (3) Repeated deprivation (RD-Alc) group given the same choice of ethanol or water for 6 weeks, followed by a twice repeated cycle of 2 weeks without ethanol followed by 2 weeks with ethanol. Two subpopulations of GLU terminals were labeled by immunostaining for the vesicular GLU transporter 1 (vGLUT1) and vesicular GLU transporter 2 (vGLUT2). DA terminals were labeled by immunostaining for tyrosine hydroxylase (TH). The GLU and DA immunostained (im) varicosities were quantified and analyzed using stereological methods. We found that chronic alcohol did not alter the number of TH-im terminals in the extended amygdala in either the C-Alc or RD-Alc drinking paradigms. Thus, the increases in extracellular levels of DA previously reported following chronic alcohol are likely due to a change in the efficiency of DA release rather than a change in the number of DA terminals. The number of vGLUT1-im terminals was also unchanged in the extended amygdala; however, the number of vGLUT2-im terminals, which represent the greater population of GLU terminals, was increased in the sNAc of the RD-Alc group compared to the Water group. Chronic alcohol is known to affect GLU release, and our findings indicate that repeated alcohol deprivation may preferentially increase GLU terminals in the sNAc bearing the vGLUT2, which are primarily afferents from the thalamus. Our results further indicate that repeated deprivation of alcohol can change the ratio of GLU to DA innervation in the sNAc, a key region of the reward circuitry.
Zhou
Feng C
FC
Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. imce100@iupui.edu
Sahr
Robert N
RN
Sari
Youssef
Y
Behbahani
Kamran
K
D000428:Alcohol Drinking / Q000503:physiopathology*; D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D008297:Male; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*
D011954:Receptors, Dopamine; D017470:Receptors, Glutamate