Electrophysiological properties of dopamine neurons in the ventral tegmental area of Sardinian alcohol-preferring rats.
BACKGROUND
Sardinian alcohol-preferring (sP) or -nonpreferring (sNP) rats are one of the few pairs of lines of rats selectively bred for their voluntary alcohol preference or aversion, respectively. Ventral tegmental area (VTA) dopamine (DA) neurons have long been implicated in many drug-related behaviors, including alcohol self-administration. However, the electrophysiological properties of these cells in sP and sNP rats remain unknown.


OBJECTIVE
This study was designed to examine the properties of posterior VTA DA neurons and to unveil functional differences between sP and sNP rats.


METHODS
The electrophysiological properties of DA cells were examined performing either single-cell extracellular recordings in anesthetized rats or whole-cell patch-clamp recordings in slices.


RESULTS
Extracellular single-unit recordings revealed an increased spontaneous activity in sP rats. However, a corresponding difference was not found in vitro. Moreover, DA cells of sP and sNP rats showed similar intrinsic properties, suggesting changes at synaptic level. Therefore, inhibitory- and excitatory-mediated currents were studied. A decreased probability of GABA release was found in sP rats. Additionally, sP rats showed a reduced depolarization-induced suppression of inhibition, which is an endocannabinoid-mediated form of short-term plasticity. Additionally, the effect of cannabinoid-type 1 (CB1) receptor agonist WIN55,212-2 on GABAA IPSCs was smaller in sP rats, suggesting either a reduced number or functionality of CB1 receptors in the VTA.


CONCLUSIONS
Our findings suggest that both decreased GABA release and endocannabinoid transmission in the VTA play a role in the increased impulse activity of DA cells and, ultimately, in alcohol preference displayed by sP rats.
Melis
Miriam
M
B.B. Brodie Department of Neuroscience, University of Cagliari, Cittadella Universitaria di Monserrato, 09042, Monserrato, Italy. myriam@unica.it
Pillolla
Giuliano
G
Perra
Simona
S
Colombo
Giancarlo
G
Muntoni
Anna Lisa
AL
Pistis
Marco
M
D000428:Alcohol Drinking; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004594:Electrophysiology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000378:metabolism
D043884:Receptor, Cannabinoid, CB1; D011963:Receptors, GABA-A; D004298:Dopamine
Biochim Biophys Acta. 2000 Dec 15;1535(1):78-86
11113634
J Neurosci. 2006 Mar 8;26(10):2788-97
16525058
Neuropsychopharmacology. 2001 Nov;25(5):651-61
11682248
J Neurosci. 1997 Jan 15;17(2):796-803
8987801
Alcohol Clin Exp Res. 2005 Mar;29(3):358-66
15770111
Am J Psychiatry. 1984 Jan;141(1):61-2
6691465
J Neurosci. 2007 May 23;27(21):5730-43
17522317
Neuropsychopharmacology. 2005 Feb;30(2):330-8
15383830
Eur J Pharmacol. 2005 Dec 5;526(1-3):251-8
16253227
Brain Res. 2003 May 30;973(2):275-84
12738071
Neuro Endocrinol Lett. 2004 Aug;25(4):235-51
15361811
Psychopharmacology (Berl). 2005 Dec;183(3):368-77
16228194
CNS Neurol Disord Drug Targets. 2006 Feb;5(1):79-97
16613555
Psychopharmacology (Berl). 2003 Jul;168(1-2):84-98
12721782
Arch Gen Psychiatry. 1995 Jan;52(1):42-52
7811161
J Neurosci Res. 2001 May 15;64(4):429-36
11340650
Arch Gen Psychiatry. 1996 Mar;53(3):199-201
8611055
J Neurosci. 2002 Mar 15;22(6):2074-82
11896147
Br J Pharmacol. 2004 Oct;143(4):455-64
15371286
J Pharmacol Exp Ther. 2005 Nov;315(2):648-57
16076936
Nat Rev Neurosci. 2004 Jun;5(6):483-94
15152198
Alcohol Clin Exp Res. 2004 Aug;28(8):1212-9
15318120
Prostaglandins Leukot Essent Fatty Acids. 2002 Feb-Mar;66(2-3):287-99
12052043
Int Rev Neurobiol. 2005;63:101-54
15797467
Alcohol Clin Exp Res. 2006 Jun;30(6):991-7
16737457
Curr Psychiatry Rep. 2001 Apr;3(2):144-51
11276410
Mini Rev Med Chem. 2007 Aug;7(8):769-79
17692039
J Neurochem. 2003 Feb;84(4):698-704
12562514
J Psychiatr Res. 1974;11:151-61
4156786
Brain Res. 1987 May;434(2):117-65
3107759
Nature. 2001 Mar 29;410(6828):588-92
11279497
Alcohol Clin Exp Res. 2002 Apr;26(4):565-74
11981134
Pharmacol Biochem Behav. 2005 Jun;81(2):369-80
15939463
Alcohol Clin Exp Res. 1998 Jun;22(4):854-7
9660312
Science. 1971 Jul 9;173(3992):123-6
4325812
J Neurochem. 1999 Feb;72(2):522-8
9930723
Brain Res. 2006 Nov 29;1122(1):135-42
17010321
Brain Res. 2002 Jan 11;924(2):242-51
11750910
Alcohol Alcohol. 2004 Jul-Aug;39(4):297-302
15208160
Brain Res. 1985 Apr 29;333(1):169-72
2859910
J Comp Neurol. 1992 Jun 8;320(2):145-60
1377716
J Neurosci. 1989 Oct;9(10):3463-81
2795134
Alcohol Alcohol. 1992 Mar;27(2):127-30
1355967
Neurosci Lett. 2007 Jun 29;421(3):270-4
17574742
Science. 2004 Mar 26;303(5666):2040-2
15044807
Brain Res. 1998 May 18;793(1-2):212-8
9630633
Drug Alcohol Depend. 2002 Mar 1;66(1):77-84
11850139
Neurochem Int. 2006 Nov;49(6):619-25
16822589
J Neurosci. 2004 Jan 7;24(1):53-62
14715937
Eur J Neurosci. 2006 Jan;23(1):205-18
16420430
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1393-8
12538878
Life Sci. 1995 Mar 3;56(15):PL261-7
8614235
Neuroscience. 1983 Oct;10(2):301-15
6633863
J Physiol. 1992 May;450:455-68
1331427
J Neurosci Res. 2000 Apr 1;60(1):122-8
10723075
Psychopharmacology (Berl). 2000 Apr;149(3):217-24
10823401
J Neurosci. 2000 Dec 1;20(23):8876-85
11102497
Trends Pharmacol Sci. 2003 Jun;24(6):266-8
12823949
Alcohol Alcohol. 2000 Mar-Apr;35(2):190-6
10787396
J Neurosci. 1999 May 15;19(10):3723-30
10234004
Handb Exp Pharmacol. 2008;(184):435-77
18064422
Alcohol Alcohol. 1993 Jul;28(4):397-400
8397521
Brain Res. 1999 Jan 2;815(1):154-66
9974136
Addict Biol. 2006 Sep;11(3-4):324-38
16961762