Dopaminergic input to GABAergic neurons in the rostral agranular insular cortex of the rat

Increasing evidence shows that the rostral agranular insular cortex (RAIC) is important in the modulation of nociception in humans and rats and that dopamine and GABA appear to be key neurotransmitters in the function of this cortical region. Here we use immunocytochemistry and path tracing to examine the relationship between dopamine and GABA related elements in the RAIC of the rat. We found that the RAIC has a high density of dopamine fibers that arise principally from the ipsilateral ventral tegmental area/substantia nigra (VTA/SN) and from a different set of neurons than those that project to the medial prefrontal cortex. Within the RAIC, there are close appositions between dopamine fibers and GABAergic interneurons. One target of cortical GABA appears to be a dense band of GABA_B receptor-bearing neurons located in lamina 5 of the RAIC. The GABA_B receptor-bearing neurons project principally to the amygdala and nucleus accumbens with few or no projections to the medial prefrontal cortex, cingulate gyrus, the mediodorsal thalamic nucleus or contralateral RAIC. The current anatomical data, together with previous behavioral results, suggest that part of the dopaminergic modulation of the RAIC occurs through GABAergic interneurons. GABA is able to exert specific effects through its action on GABA_B receptor-bearing projection neurons that target a few subcortical limbic structures. Through these connections, dopamine innervation of the RAIC is likely to affect the motivational and affective dimensions of pain.