Effects of nicotine exposure on oral methamphetamine self-administration, extinction, and drug-primed reinstatement in adolescent male and female rats.

BACKGROUND: Adolescent nicotine exposure increases methamphetamine (MA) intake in adult male rats; however, little is known about how nicotine affects MA self-administration during the adolescent period. Therefore, we assessed whether exposing rats to nicotine during early or late adolescence affects oral MA self-administration. METHODS: 146 male and female rats were treated with saline or nicotine (0.16 or 0.64 mg/kg) from postnatal day (PD) 25-PD 34 (the early exposure phase) and/or PD 35-PD 55 (the late exposure phase). Rats began an oral MA self-administration procedure on PD 35. RESULTS: Only the sex variable, but not nicotine, affected sucrose and MA acquisition, as female rats had more nose pokes than males during training. On the test sessions, female rats exposed to nicotine (0.64 mg/kg) in the early exposure phase had more active nose pokes than saline-treated female rats or nicotine-treated male rats. Rats exposed to nicotine (0.16 mg/kg) in the late exposure phase had fewer active nose pokes during testing than rats exposed to saline. Nose poke responding during extinction was not altered by nicotine exposure, but administering nicotine (0.16 or 0.64 mg/kg) to male rats in the early exposure phase did decrease nose pokes during the drug-primed reinstatement session. CONCLUSIONS: Our results show that adolescent female rats are more sensitive to the reinforcing effects of oral sucrose and MA than adolescent males, and that preadolescent nicotine exposure enhances oral MA self-administration in female rats. These findings suggest that preteen nicotine use may increase vulnerability to later MA abuse in teenage girls.

Effects of acute or repeated paroxetine and fluoxetine treatment on affective behavior in male and female adolescent rats.

RATIONALE: The SSRI antidepressant fluoxetine is one of the few drugs that is effective at treating depression in adolescent humans. In contrast, the SSRI paroxetine has limited efficacy and is more at risk for inducing suicidal behavior. OBJECTIVE: The purpose of the present study was to more fully characterize the differential actions of paroxetine and fluoxetine. METHODS: In experiment 1, male and female rats were injected with paroxetine (2.5 or 10 mg/kg), fluoxetine (10 mg/kg), or vehicle for 10 days starting on postnatal day (PD) 35, and affective behaviors were assessed using sucrose preference and elevated plus maze tasks. A separate set of rats were used to examine monoamine levels. In experiment 2, rats were injected with paroxetine (2.5, 5, or 10 mg/kg), fluoxetine (5, 10, or 20 mg/kg), or vehicle during the same time frame as experiment 1, and anxiety-like behaviors were measured using elevated plus maze, light/dark box, and acoustic startle. RESULTS: Repeated SSRI treatment failed to alter sucrose preference, although both paroxetine and fluoxetine reduced time spent in the open arms of the elevated plus maze and light compartment of the light/dark box. Paroxetine, but not fluoxetine, enhanced acoustic startle and interfered with habituation. Serotonin turnover was decreased by both acute and repeated fluoxetine treatment but unaltered by paroxetine administration. DISCUSSION: These results show that repeated treatment with paroxetine and fluoxetine has dissociable actions in adolescent rats. In particular, paroxetine, but not fluoxetine, increases acoustic startle at low doses and may increase sensitivity to environmental stressors.