Impact of repeated methamphetamine pretreatment on intravenous self-administration of the drug in males and estrogenized or non- estrogenized ovariectomized female rats.

OBJECTIVE: The female animals were already recorded to respond differently to methamphetamine (MET) abuse than males. This gender dissimilarity may be caused by the influence of estral cycles and different susceptibility to behavioural sensitization.

METHODS: Influences of gender and pre-exposure to MET were studied in the rat model of MET intravenous self-administration (IVSA). The fixed ratio (FR) paradigm was employed in male rats (M) and estrogenized (F-ESTR) and non-estrogenized ovariectomized female rats (F-OVX) either pre-exposed or not-exposed to MET pretreatment.

RESULTS: In rats that were not pre-exposed to MET, F-ESTR self-administered more MET infusions than each of the other groups, but F-OVX self-administered less than each of the other groups; the same trend was apparent in the MET pretreated groups. MET pre-exposure decreased subsequent MET IVSA in all groups except F-OVX.

CONCLUSION: Thus, pre-exposure to MET and the loss of inherent estrogen in females notably decreased the intake of MET by rats, suggesting that abuse liability was reduced. Estrogen's effects on MET self-administration here correspond with accumulating evidence of stronger behavioural responses of females to drugs of abuse.