We compared the effects of single intraveinous injection of pituitary adenylate cyclase-activating polypeptide-38 (P38) to those of its analog, acetyl-[Ala15, Ala20]PACAP-38-propylamide (P38-alg) on spatial memory in the Morris water maze (MWM) using a weak massed-learning procedure, post-training brain derived neurotrophic factor (BDNF) and post-training oxidative stress biomarker assays in male Wistar rats. Acquisition of the MWM task following P38 (30 μg/kg) and P38-alg (30 μg/kg) treatments was similar to control group (Saline: 0.9% NaCl) and there was no interaction between treatments and performance. However, in the probe test, P38-treated group showed a specific interest for the target quadrant whereas the two other groups exhibited less focused place searching behavior. Moreover, P38 had an anxiogenic effect as measured by the distribution of swimming at the periphery of the pool. The swimming test resulted in a decrease in BDNF contents in the hippocampus. P38 but not P38-alg treatment restored BDNF expression. In terms of oxidative stress, both P38 and P38-alg treatments had antioxidative effects. The activity of antioxidative enzymes in the neocortex was increased. However only P38 reduced the levels of carbonylated proteins (CP). These data show that P38 and P38-alg have different behavioral and neurobiological effects. Thus, P38-alg and other analogs with specific functional profiles, inducing beneficial central effects (e.g. neuroprotection) while minimizing undesired peripheral effects may be useful for potential therapeutical use.