Amygdalar opioids modulate hypothalamic melanocortin-induced anorexia

Abstract

We wanted to assess the possibility that opioid activity in the central amygdala (CeA) could modulate the feeding inhibition of melanocortin stimulation of the paraventricular hypothalamus (PVN). The melanocortin system is important in both the acute regulation of satiety and feeding behavior and in the integration of long-term appetite signals. Melanotan II (MTII) is a synthetic MC3R and MC4R agonist which reduces food intake when given intracerebroventricularly (ICV) and into the PVN. Tyr-D-Ala-Gly-(me) Phe-Gly-ol (DAMGO), a micro-opioid receptor agonist, increases food intake, while opioid antagonists, like naltrexone (NTX), inhibit food intake after injection into many brain sites involved in appetite regulation, including the CeA. In food-deprived male Sprague-Dawley rats, co-injected intra-PVN MTII partially blocked the orexigenic effect of co-injected intra-CeA DAMGO. Intra-CeA NTX co-injected with intra-PVN MTII reduced food intake significantly more than either alone. NTX administered intra-CeA reduced c-Fos-immunoreactivity (IR) in nucleus accumbens neurons significantly compared to the intra-PVN MTII treated animals, animals co-injected intra-PVN with MTII and intra-CeA with NTX animals, and control animals. Intra-PVN MTII induced c-Fos-IR in significantly more PVN neurons than observed in control animals. Intra-CeA NTX co-injected with intra-PVN MTII induced c-Fos-IR significantly in PVN neurons relative to control and intra-CeA NTX animals. Such data support the significance of opioid action within the CeA as a modulator of the feeding regulation action of melanocortins within the PVN, occurring within the context of a larger appetitive network.

Fig. 1

The effects of co-injection of MTII and DAMGO on mean (± SE) food intake at 1, 2, and 4 hours. *denotes significantly decreased feeding at P < 0.05. **denotes significantly increased feeding at P < 0.05.

Fig. 2

The effects of co-injection of MTII and NTX on mean (± SE) food intake at 1, 2, and 4 hours. *denotes significantly decreased feeding at P < 0.05. **denotes significant difference at P < 0.05.

Fig. 3

Mean (± SE) number of c-Fos-immunoreactive (c-Fos-IR) nuclei in the PVN after co-injection of intra-PVN MTII 50 pmol and intra-CeA NTX 79 nmol (* P < 0.05).

Fig. 4

Mean (± SE) number of c-Fos-immunoreactive (c-Fos-IR) nuclei in the Acb after co-injection of intra-PVN MTII 50 pmol and intra-CeA NTX 79 nmol (* P < 0.05).