The present study demonstrated the enhancing effect of LBP on male sexual behavior in rats. In both experiments 1 and 2, the CE, EF and EL were improved by LBP and only IL was also improved in experiment 2. The effects of LBP appeared to enhance both motivation (indicated by IL) and copulatory performance (indicated by CE, EF and EL) 
. Furthermore, it is shown that the improved sexual performance was associated with increased neurogenesis in the two neurogenic zones, suggesting that neurogenesis may be associated with the sexual-enhancing effects of LBP. The causal relationship between neurogenesis and sexual behavior was demonstrated in experiment 3, in which the sexual-enhancing effect of LBP was abolished by blocking neurogenesis.
Wolfberry has been prescribed for treating male infertility for a long history, although there is a scarcity of scientific evidence for this indication 
. Recently a study revealed that an improved subjective view on sexual ability was found in subjects chronically consumed a juice prepared from wolfberry 
. This study suggests the potential clinical use of wolfberry to improve male sexual performance.
The findings of the present study showed the sexual-enhancing effect of LBP from a pre-clinical point of view. Our results showed that the beneficial effect was not only revealed in normal, healthy rats, but also in rats with sexual inhibition induced by corticosterone. The ‘rescuing’ effect of LBP on male sexual behavior suggests that LBP may be useful to treat male sexual dysfunction. This notion agrees with previous studies in which castration and irradiation on reproductive tissues suppressed male mating behavior, while LBP improved the mating ability of the affected rats 
. Apart from behavioral aspect, LBP may exert its beneficial effects on the reproductive system at cellular level. For example, LBP was found to protect spermatogenic cells from apoptosis induced by hyperthermia and the structural integrity of the seminiferous epithelium could be preserved by LBP 
. In short, the sexual-enhancing effect of LBP may be multi-faceted, ranging from protection of gametes against harmful insults to enhancement of individual sexual behavior. Thus, how does LBP benefit reproduction may warrant further investigations.
The relationship between neurogenesis and sexual behavior shown in this study suggests that neurogenesis may be involved in copulation, and neurogenesis could be one of the mechanisms of how LBP exerts its pro-sexual effect. Neurogenesis could be found at different brain regions while the two most prominent neurogenic regions are the SVZ and hippocampus 
. Neural progenitor cells proliferate at the SVZ and migrate tangentially along the rostral migratory stream (RMS) to reach the olfactory bulb, which allows continuous addition of new neurons for formation of new circuits throughout the adulthood in rodents 
. The renewal of interneurons in the olfactory bulb renders the ability of olfactory learning, including differentiating sex-related olfactory signals 
. As the hippocampus is well recognized for its necessity in memory formation
, it may also take part in the formation of memory regarding the processing of sexual cues 
Previous studies outlined the interrelationship between adult neurogenesis and sexual behavior. For instance, exposure of female prairie voles or ewes to males increased neurogenesis in the SVZ and hippocampus 
. Another study showed that newborn cells in the olfactory bulbs integrated into the ‘mating’ circuit and could be activated by estrus female pheromones 
. More recent studies showed that neurogenesis is essential for the display of normal sexual behaviors in both female and male rodents 
. Under normal situation, female mice prefer to mate with dominant males. When the neurogenesis in the SVZ and hippocampus were blocked by cytostatic cytosine arabinoside, the preference was then abolished 
. On the other hand, when neurogenesis was suppressed in male rats, the sexual performance was impaired 
. The decreased neurogenesis was associated with a decrease in neuronal activation in mating-related circuits, which may be the reason underlying the sexual inhibition. The present study further showed that blocking neurogenesis could abolish the sexual-enhancing effect of LBP. These observations indicate that adult neurogenesis warrants the reproductive success of rodents, and disruption of it would cause dysfunction in sexual behavior. In the present data, corticosterone suppressed both neurogenesis and sexual performance simultaneously while LBP could prevent these from occurring. The neurogenesis promoting effect of LBP was further confirmed in the in vitro
assays, in which the corticosterone-induced proliferation inhibition 
was reversed by LBP. Apart from cell proliferation, LBP also promotes the neuronal differentiation of neural precursor cells as shown by DCX staining. The neurogenic effect of LBP agrees with previous findings 
. Interestingly, the sexual performance was found to correlate with neurogenesis. These findings provide further evidence to support the notion that the newborn neurons participate in sexual behavior. Furthermore, neurogenesis in the SVZ and hippocampus are correlated with different measurements in the sexual behavior test, which implies that SVZ neurogenesis may be intimately involved in sexual motivation (indicated by ML/IL) while both the SVZ and hippocampus are involved in copulatory performance. Further studies are required to explore this possibility and this may provide insight on the neural basis of reproductive biology.
Previous studies have shown a dose-dependent response of LBP treatment on neuroprotection 
and sexual behavior 
. We choose the current dosages (1 mg/kg and 10 mg/kg) since it was reported that the maximum therapeutic effect could be achieved by these two dosages 
. Previous reports showed that high dose of LBP inhibited c-jun N-terminal kinase (JNK) pathway 
, which may subsequently inhibit neural stem cell proliferation 
. This may be the potential mechanism of loss of neurogenesis and sexual-enhancing effect of LBP at high dosage, while this would be confirmed in future studies.
It should be noted that neurogenesis consists of different stages including cell proliferation, differentiation, migration, survival and incorporation of new neurons into the existing neural circuit 
. The current study investigated the early phases including cell proliferation and differentiation, while later phases were not studied. While newly proliferated cells may act as a source of trophic factors which affect functioning of other neurons, much matured new neurons may directly involve in signal transduction. Further studies of the effect of LBP on the later phases, which may extend the treatment period to over eight weeks, may suggest its long term effect on sexual behavior of the animal from the view of neurogenesis.
LBP may also modulate sexual behavior via increasing the expression of testosterone in sexually inhibited animals. Our results show that chronic corticosterone significantly suppressed the plasma level of testosterone; and thus resulting in inhibited sexual performance. Concomitance to enhancing the sexual performance, LBP also reverse the decrease in testosterone level. Similar result was found by Luo et. al. 
that LBP increased the testosterone levels in rats subjected to castration or irradiation on testis. Alternatively, as it is recently reported that antioxidant could increase the sexual motivation 
, LBP may enhance sexual behavior through its antioxidant property 
To conclude, this study provides evidence for the pro-sexual effect of LBP in both normal animals and animals with suppressed sexual performance. Such findings support the use of wolfberry as a treatment for sexual dysfunction or as an aphrodisiac treatment. LBP could also reverse the decreased neurogenesis induced by corticosterone, which is a possible mechanism underlying its effect. Further exploration on the mechanisms would provide stronger rationale for the use of wolfberry in clinical situations. Furthermore, the effect of wolfberry on female sexual function is not yet explored. Future test of LBP on female rodent models may provide insight on the potential usage of wolfberry on treating female sexual dysfunction, such as sexual desire or arousal disorders.