GABAA and GABAB receptors in the nucleus accumbens shell differentially modulate dopamine and acetylcholine receptor-mediated turning behaviour

The ability of GABA(A) and GABA(B) receptors in the shell of the nucleus accumbens to modulate distinct types of turning behaviour was investigated in freely moving rats, using the unilateral injection technique. The GABAA receptor agonist muscimol and the GABA(A) receptor antagonist bicuculline did not produce turning behaviour; the same holds for the GABA(B) agonist baclofen and the GABA(B) antagonist 2-hydroxysaclofen. A mixture of the dopamine D-1 receptor agonist SKF 38393 and the dopamine D-2/3 receptor agonist quinpirole has been found to elicit contraversive pivoting, when injected into the shell. This pivoting was dose-dependently inhibited by muscimol, and the inhibitory effect of muscimol was antagonised by bicuculline. Pivoting was also dose-dependently inhibited by baclofen; however, 2-hydroxysaclofen did not antagonise the inhibitory effect. The acetylcholine receptor agonist carbachol has been found to elicit contraversive circling, when injected into the shell. This carbachol-induced circling was inhibited by baclofen, and 2-hydroxysaclofen antagonised the inhibitory effect. Carbachol-induced circling was also partially inhibited by muscimol; however, the inhibitory effect of muscimol was not antagonised by bicuculline. It is concluded that mesolimbic GABA(A) receptors exert an inhibitory control on dopamine-dependent pivoting that call be elicited from the shell of the nucleus accumbens, and that GABA(B) receptors exert all inhibitory control on acetylcholine-dependent circling that call be elicited from the shell of the nucleus accumbens. This data extends the earlier reported findings that the neurochemical substrate in the shell of the nucleus accumbens that mediates dopamine-dependent pivoting is fundamentally different from the shell substrate that mediates acetylcholine-dependent circling. (C) 2004 Elsevier Ltd. All rights reserved.