Summary GABA release from interneurons in VTA, projections from the nucleus accumbens (NAc) and rostromedial tegmental nucleus (RMTg) was selectively activated in rat brain slices. The inhibition induced by μ-opioid agonists was pathway dependent. Morphine induced a 46% inhibition of IPSCs evoked from the RMTg, 18% from NAc and IPSCs evoked from VTA interneurons were almost insensitive (11% inhibition). In vivo morphine treatment resulted in tolerance to the inhibition of RMTg inputs, but not local interneurons or NAc inputs. One common sign of opioid withdrawal is an increase in adenosine-dependent inhibition. IPSCs evoked from the NAc were potently inhibited by activation of presynaptic adenosine receptors, whereas IPSCs evoked from RMTg were not changed. Blockade of adenosine receptors selectively increased IPSCs evoked from the NAc during morphine withdrawal. Thus, the acute action of opioids, the development of tolerance, and the expression of withdrawal are mediated by separate GABA afferents to dopamine neurons.

SUMMARY Food aversions develop when the taste of a novel food is associated with sickness, which often occurs after food poisoning or chemotherapy treatment. We identified calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) as sufficient and necessary for establishing a conditioned taste aversion (CTA). Photoactivating projections from CGRPPBN neurons in either the central nucleus of the amygdala or the bed nucleus of the stria terminalis can also induce robust CTA. CGRPPBN neurons undergo plasticity following CTA and inactivation of either Arc or Grin1 (genes involved in memory consolidation), prevents establishment of a strong CTA. Calcium imaging reveals that the food reactivates CGRPPBN neurons after conditioning. Inhibition of these neurons or inactivation of the Gril1 gene after conditioning attenuates CTA expression. Our results indicate that CGRPPBN neurons not only play a key role for learning food aversions, but also contribute to the maintenance and expression of those memories.

Sodium-depleted animals develop an appetite for aversive concentrations of sodium. Here we show that chemogenetic activation of aldosterone-sensitive neurons that express 11β-hydroxysteroid dehydrogenase type 2 (HSD2) in the nucleus of the solitary tract is sufficient to drive consumption of sodium-containing solutions in mice, independently of thirst or hunger. These HSD2-positive neurons are necessary for full expression of sodium appetite and have distinct downstream targets that are activated during sodium depletion.