Oxycodone-induced dependence modifies BDNF levels within the fronto-cerebellar circuitry in adult male rats

Introduction: Recent studies support the involvement of the cerebellum in addiction. Opioid receptors mu- and kappa-varieties are present in the cerebellum; nonetheless, the effects of oxycodone in the cerebellum are unknown. Brain-Derived Neurotrophic Factor (BDNF), the precursor proBDNF, and the matureBDNF regulate opioid induced-plasticity in the mature brain; thus, it may be pivotal in oxycodone rewarding properties and responses.

Aim: determine the effects of oxycodone induced-conditioned place preference (CPP) on levels of Pro-BDBF/mature-BDNF in the prefrontal cortex and cerebellum. On PND120, male adult rats were tested for CPP after being randomly assigned to the oxycodone drug group (four daily 20-min pairings with oxycodone (3 mg/kg, s.c.) and four daily pairings with saline on alternate days) or the vehicle group (eight 20-min pairings with saline). Following conditioning, rats were given a 20-min CPP test for evaluating oxycodone preference. After the preference test, brains were collected and analyzed for Pro and Mature BDNF levels with an immunoassay (ELISA).

Results: oxycodone induced CPP [ F (1, 21) = 55.02, p < .001]. Furthermore oxycodone induced-CPP increased levels of Pro-BDNF in the PFC [F (1, 21) = 14.46 p<.001] and decreased levels in the cerebellum [ F (1, 21) = 7.82, p < .01].

Conclusions: Oxycodone CPP modified Pro-BDNF levels in a “seesaw” mechanism in the fronto-cerebellar circuitry. Thus, pro-BDNF may be required neurotrophins in the opioid-induced reorganization of fronto-cerebellar circuitry and fronto-cerebellar dysfunction.