Tamoxifen disrupts consolidation and retrieval of morphine-associated contextual memory in male mice: interaction with estradiol

Abstract

Rationale: Tamoxifen (TMX), a selective estrogen receptor modulator, can affect cognitive functions of the brain. The conditioned place preference (CPP) paradigm involves memory for the association between contextual cues and the rewarding properties produced by a drug.

Objectives: The effects of TMX alone and in combination with estradiol (E2) on reward-related memory of morphine were investigated in adult male mice.

Materials and methods: Using an unbiased CPP paradigm, the ability of morphine sulfate (0.5-10 mg/kg, s.c.) to produce CPP was studied. Afterwards, the effects of TMX (1-10 mg/kg, s.c.) on the acquisition, consolidation, and expression of morphine-induced CPP were assessed. We have also evaluated the possible effects of s.c. E2 (10-200 mug/kg) and its co-administration with TMX (10 mg/kg, s.c.) on the consolidation and retrieval of morphine-associated contextual memory.

Results: (1) Morphine (0.5-10 mg/kg) significantly induced CPP in a dose-dependent manner. (2) TMX (10 mg/kg) significantly reduced the time spent by mice in the morphine compartment when given immediately after each conditioning session (consolidation) or 30 min before testing for place preference in the absence of morphine (expression), whereas it had no effect when administered 30 min before each training session (acquisition). (3) Post-training or pre-testing administration of E2 increased morphine-induced CPP in a dose-dependent manner. (4) In addition, concomitant administration of E2 with TMX appears to prevent the impairing effect produced by TMX.

Conclusions: TMX appears to disrupt consolidation and retrieval of morphine-associated contextual memory and this impairing effect might be prevented by E2 treatment.