Nicotine sensitization (part 1): estradiol or tamoxifen is required during the induction phase and not the expression phase to enable locomotor sensitization to nicotine in female rats.

RATIONALE

Nicotine sensitization involves two functionally distinct phases: induction and expression. Estradiol enhances nicotine sensitization in female rats, but it is not known whether this enhancement is specific to one or both phases.

OBJECTIVES

We investigated the effects of estradiol selectively during the induction and the expression of nicotine sensitization.

METHODS

Ovariectomy (OVX) rats were administered E2 during the induction (2 injection days) and/or the expression phase (9 days later) of nicotine sensitization. The selective estrogen receptor modulator tamoxifen (agonist of ERα and ERß, agonist of the g-coupled estradiol receptor GPER1) also was used to elucidate receptor candidates for the effects of E2 on nicotine sensitization.

RESULTS

Gonadally intact female rats exhibited expression of nicotine sensitization after a 9-day delay, whereas OVX females did not. Administration of E2 limited to the induction phase of nicotine sensitization rescued expression of nicotine sensitization in OVX females. Tamoxifen during induction did not alter expression of sensitization in gonadally intact female rats, and, like E2, was sufficient to reverse the dampening effects of OVX on expression of sensitization.

CONCLUSIONS

The enhancing effects of E2 on nicotine sensitization occur during the induction phase of nicotine sensitization, although require a delay to produce the effects on locomotor activity to nicotine, and may involve non-canonical estrogen pathways (e.g., activation of GPER1).