The mediodorsal nucleus of the thalamus in rats .2. Behavioral and neurochemical effects of GABA agonists

The aim of this study was to determine how GABA receptors in the mediodorsal nucleus of the thalamus in rats might contribute to the regulation of locomotor behavior. Microinjections of the GABA(B) and GABA(A) agonists, baclofen and muscimol, into the mediodorsal nucleus produced dose-dependent increases in locomotion that were blocked by co-administration of the GABA(B) antagonist, 2-hydroxysaclofen. Microinjection of baclofen along the midline, lateral into the ventrolateral thalamus or into the lateral ventricles produced significantly smaller dose-dependent increases in locomotion, indicating that the anatomical locus for baclofen-induced locomotion resides in the mediodorsal nucleus. The motor response elicited by microinjected baclofen was associated with a reduction in dopamine metabolism in the prefrontal cortex and an increase in metabolism in the core of the nucleus accumbens, but not in the accumbal shell or the dorsolateral striatum. These results suggest that GABAergic afferents to the mediodorsal nucleus may oppose a tonic inhibitory tone on locomotor activity. The data also suggest that the motor response produced by baclofen in the mediodorsal thalamus may arise by inhibiting the projections to the prefrontal cortex which modulate mesocorticolimbic dopamine transmission.