The modulating effects of rottlerin on psychostimulant-induced conditioned place preference

Abstract

Three cocaine (10 mg/kg/conditioning COC)- and methamphetamine (1 mg/kg/conditioning MA)-place conditionings reliably established the drug-induced conditioned place preference (CPP) in 8-week-old male C57BL/6 mice An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 hrs prior to the first COC- and MA-place conditioning prevented the establishment of COC and MA-induced CPP Following the establishment of the COC- and MA-induced CPP three consecutive daily saline-place conditionings were used to extinguish mouse CPP performance A single rottlerin injection (5 mg/kg i p ) 20 hrs prior to the first saline-place conditioning bout did not affect such conditionings-produced CPP extinction but diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP Omitting the extinction conditionings a single rottlerin injection (5 mg/kg) did not cause the conditionings-produced CPP extinction A single rottlerin (5 mg/kg i p ) treatment produced fast-onset and long-lasting increases in hippocampal BDNF levels while such a treatment did not alter ERK and CREB phosphorylation in the hippocampus Pretreatment with a BDNF TrkB receptor antagonist K252a (5 ?g/kg) did not affect rottlerin’s suppressing effect on cocaine-induced CPP Treatment with 7 8-dihydroxyflavone (10 mg/kg x 6) a selective TrkB agonist prior to each conditioning bout did not affect COC-induced CPP Based on these results suggest that systemic rottlerin treatment may be beneficial in facilitating the erasure of COC and MA-supported memory Importantly such a treatment may afford a therapeutic advance in corroborating the extinction training-caused forgetting of the COC and MA-supported memory However rottlerin-produced brain BDNF increases play a negligible role in mediating its effects on the formation and maintenance of psychostimulant-supported memory in this regard

Date of Award	2015 Aug 21
Original language	English
Supervisor	Lung Yu (Supervisor)