Neuropeptide Y (NPY) is one of the most abundant
peptides in mammalian brain and NPY-like-immunoreactivity is highly expressed in the lateral septum, an area extensively involved in anxiety regulation. NPY counteracts the neurochemical and behavioral responses to acute threat in animal models, and intracerebroventricular (i.c.v.) administration of NPY at low doses is
anxiolytic. Less is known about the specific contributions of the lateral septum to NPY-mediated anxiety regulation. In Experiment 1, the effects of infusions of NPY (1.5 μg) into the lateral septum were investigated in three animal models of anxiety: the elevated plus-maze, novelty-induced suppression of feeding, and
shock-probe burying tests. Experiment 2 examined the role of the NPY Y1 receptor in these models by co-infusing the Y1 antagonist
BIBO 3304 (0.15 μg, 0.30 μg) with NPY into the lateral septum. In the elevated plus-maze, there were no changes in rats' open arm exploration, the index of anxiety reduction in this test. In the novelty-induced suppression of feeding test, rats infused with NPY showed decreases in the latency to consume a palatable snack in a novel (but not familiar) environment, suggesting a reduction in anxiety independent of increases in appetite. This anxiolysis was attenuated by co-infusion with
BIBO 3304 (0.30 μg) in Experiment 2. Lastly, rats infused with NPY showed decreases in the duration of burying behavior in the
shock-probe burying test, also indicative of anxiety reduction. However, unlike in the feeding test,
BIBO 3304 did not attenuate the NPY-induced anxiolysis in the
shock-probe test. It is concluded that NPY produces
anxiolytic-like actions in the lateral septum in two animal models of anxiety: the novelty-induced suppression of feeding, and
shock-probe burying tests, and that this anxiolysis is dependent on Y1 receptor activation in the feeding test.