Analgesic and anxiolytic effects of [Leu³¹,Pro³⁴]-neuropeptide Y microinjected into the periaqueductal gray in rats

Several reports have demonstrated that neuropeptide Y (NPY) is involved in food intake, epilepsy, circadian rhythms, drug seeking, pain and anxiety, and other physiological or pathological conditions. On the other hand, periaqueductal gray (PAG) is a key brain center for modulating pain, anxiety and fear. It is the main structure implicated in integrated defensive behaviors. One such behavior, tonic immobility (TI), resembles fear and is able to induce analgesia. After microinjection of [Leu³¹,Pro³⁴]-Neuropeptide Y ([Leu³¹,Pro³⁴]-NPY) into the PAG dorsal (D) or ventrolateral (VL) of adult male Wistar rats, the following parameters were assessed: i) the analgesic effect by means of the tail-flick test (TF), ii) the duration of TI as a passive defensive behavioral response and as an anxiety/fear model (considering both TF and TI as single behaviors), iii) TI-induced analgesia by the combination of TF/TI, and iv) the anxious-like state through the elevated plus maze (EPM), and defensive burying behavior (DBB). The results show that the microinjection of [Leu³¹,Pro³⁴]-NPY into the PAG produced an analgesic effect (increasing the TF latency); overall decreased the TI duration, which might represent an important anti-fear effect. Moreover, [Leu³¹,Pro³⁴]-NPY microinjected into the PAG allows for a TI-induced analgesic effect, as well as, a substantial anxiolytic effect (evidenced by the EPM and DBB models). Hence, [Leu³¹,Pro³⁴]-NPY microinjected into the PAG, especially at 0.47 nmol/0.5 μL produces both analgesic and anxiolytic effects, in a higher magnitude within ventrolateral area.