Rationale 18-Methoxycoronaridine (18-MC), a selective antagonist of α3β4 nicotinic receptors, has been previously shown, in rats, to reduce the self-administration of several drugs of abuse, reduce operant responding for sucrose, and prevent the development of sucrose-induced obesity. It has become increasingly apparent that there is a significant overlap between the systems regulating drug reward and food intake, therefore, we investigated whether 18-MC might modulate the effects of ghrelin, one of several orexigenic peptides recently implicated in both feeding and drug reward. Objectives In female Sprague–Dawley rats, we determined whether acute 18-MC treatment would reduce both ghrelin-induced increases in sucrose intake and ghrelin-elicited increases in accumbal dopamine levels. Results Pretreatment with 18-MC (20 mg/kg, i.p.), given prior to the administration of ghrelin (1 µg, lateral ventricle), blocked ghrelin-induced increases in sucrose (5%) intake in a two-bottle open access paradigm. Using in vivo microdialysis, 18-MC (both 20 and 40 mg/kg) prevented ghrelin (2 µg, intraventral tegmental area)-induced increases in extracellular dopamine in the nucleus accumbens. 18-MC had no effect on deposition of fat or on serum levels of glucose, triglycerides, and cholesterol in ghrelin-treated rats. Conclusions The present results suggest that one potential mechanism by which 18-MC exerts its effects on palatable food consumption is via modulation of ghrelin’s effects.

Early visual experience and innate developmental programs interact to shape cortical circuits. Visual-deprivation experiments have suggested that the onset of visual experience determines when interneurons mature in the visual cortex. Here we used neuronal transplantation and cellular imaging of visual responses to investigate the maturation of parvalbumin-positive (PV) interneurons. Our results suggest that the emergence of broad orientation selectivity in PV interneurons is innately timed.

The maturation of cortical parvalbumin-positive (PV) interneurons depends on the interaction of innate and experience-dependent factors. Dark-rearing experiments suggest that visual experience determines when broad orientation selectivity emerges in visual cortical PV interneurons. Here, using neural transplantation and in vivo calcium imaging of mouse visual cortex, we investigated whether innate mechanisms contribute to the maturation of orientation selectivity in PV interneurons. First, we confirmed earlier findings showing that broad orientation selectivity emerges in PV interneurons by 2 weeks after vision onset, ϳ35 d after these cells are born. Next, we assessed the functional development of transplanted PV (tPV) interneurons. Surprisingly, 25 d after transplantation (DAT) and Ͼ2 weeks after vision onset, we found that tPV interneurons have not developed broad orientation selectivity. By 35 DAT, however, broad orientation selectivity emerges in tPV interneurons. Transplantation does not alter orientation selectivity in host interneurons, suggesting that the maturation of tPV interneurons occurs independently from their endogenous counterparts. Together, these results challenge the notion that the onset of vision solely determines when PV interneurons become broadly tuned. Our results reveal that an innate cortical mechanism contributes to the emergence of broad orientation selectivity in PV interneurons.