Cocaine- and amphetamine-regulated transcript peptide- and dopamine-containing systems interact in the ventral tegmental area of the zebra finch, Taeniopygia guttata, during dynamic changes in energy status

The mesolimbic dopamine (DA)-pathway regulates food-reward, feeding-related behaviour and energy balance. Evidence underscores the importance of feeding-related neuropeptides in modulating activity of these DA neurons. The neuropeptide, CART, a crucial regulator of energy balance, modulates DA-release, and influences the activity of ventral tegmental area (VTA) DAergic neurons in the mammalian brain. Whether CART- and DA-containing systems interact at the level of VTA to regulate energy balance, however, is poorly understood. We explored the interaction between CART- and DA-containing systems in midbrain of the zebra finch, Taeniopygia guttata, an interesting model to study dynamic changes in energy balance due to higher BMR/daytime body temperature, and rapid responsiveness of the feeding-related neuropeptides to changes in energy state. Further, its midbrain DA-neurons share similarities with those in mammals. In the midbrain, tyrosine hydroxylase-immunoreactive (TH-i) neurons were seen in the substantia nigra (SN) and VTA [anterior (VTAa), mid (VTAm) and caudal (VTAc)]; those in VTA were smaller. In the VTA, CART-immunoreactive (CART-i)-fibers densely innervated TH-i neurons, and both CART-immunoreactivity (CART-ir) and TH-immunoreactivity (TH-ir) responded to energy status-dependent changes. Compared to fed and fasted birds, refeeding dramatically enhanced TH-ir and the percentage of TH-i neurons co-expressing FOS in the VTA. Increased prepro-CART-mRNA, CART-ir and a transient appearance of CART-i neurons was observed in VTAa of fasted, but not fed birds. To test the functional interaction between CART- and DA-containing systems, ex-vivo superfused midbrain-slices were treated with CART-peptide and changes in TH-ir analysed. Compared to control tissues, CART-treatment increased TH-ir in VTA but not SN. We propose that CART is a potential regulator of VTA DA-neurons and energy balance in T. guttata.