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Table 1.

Time schedule of experiments.

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Figure 1.

Effect of fluoxetine on body weight in adolescent and adult rats.

Data are presented as mean ± S.E.M. body weight (g) in adolescent rats (A) and adult (B) rats (n = 10). 21 Days of fluoxetine treatment had no effect on bodyweight of adolescent rats, but reduced bodyweight in adult rats. *p<0.05 fluoxetine versus methylcellulose in age group.

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Figure 2.

Effect of fluoxetine on exploratory behavior in adolescent and adult rats.

Data are presented as mean ± S.E.M. of distance moved within 60 min (n = 10). 7 Days following chronic fluoxetine treatment (12 mg/kg) exploratory behavior in the open field was not affected in adolescent, nor adult, rats. ap<0.05 main age effect.

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Figure 3.

Effect of fluoxetine treatment on anxiety in adolescent and adult rats.

Data are presented as mean ± S.E.M. of time spent in the open of the elevated plus maze (n = 10). 10 Days following chronic fluoxetine treatment (12 mg/kg) anxiety in the elevated plus maze test was increased in both adolescent and adult rats. #p<0.05 main treatment effect.

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Figure 4.

Effect of fluoxetine treatment on behavioral despair in adolescent and adult rats.

Data are presented as mean ± S.E.M. of time spent on immobility (n = 10). 10 Days following chronic fluoxetine treatment (12 mg/kg) behavioral despair, expressed as immobility in the forced swim test, was increased in adolescent, but unaffected in adult rats. ap<0.05 main age effect; p<0.05 age x treatment interaction; *p<0.05 fluoxetine versus methylcellulose in age group.

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Figure 5.

Effect of fluoxetine treatment on the startle reflex and PPI in adolescent and adult rats.

Data are presented as mean ± S.E.M. of the startle reflex (n = 10; A) and PPI (n = 9; B). 7 Days following chronic fluoxetine treatment (12 mg/kg) the acoustic startle response was reduced in adult, but not adolescent rats. Fluoxetine had no significant effects on PPI. ap<0.05 main age effect; #p<0.05 main treatment effect; *p<0.05 fluoxetine versus methylcellulose in age group.

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Figure 6.

Effect of fluoxetine treatment on the awake state, non-REM sleep, spindles, and REM sleep in adolescent and adult rats.

Data are presented as mean ± S.E.M. minutes time spent in the awake state (A), non-REM sleep (B), spindles (C), and REM sleep (D) (n = 4–7). These states were measured at four time intervals: 17.30–18.30 p.m., 19.30–20.30 p.m., 5.30–6.30 a.m. and 7.30–8.30 a.m. Rats were housed under a reversed 12 hr day/light cycle, with lights on at 19.00 p.m. 14–17 Days following chronic fluoxetine treatment (12 mg/kg) wakefulness was increased and non-REM sleep was decreased in adult, but not adolescent rats during the 17.30–18.30 p.m. interval. p<0.05 age x treatment interaction; ap<0.05 age effect; *p<0.05 fluoxetine effect significantly different from methylcellulose effect.

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Table 2.

Fluoxetine (ng/ml) and norfluoxetine (ng/ml) levels in blood plasma.

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Figure 7.

The relative optical density of 5-HT1A receptor immunostaining in the dorsal raphe nucleus, mPFC, and amygdala of fluoxetine and methylcellulose treated adolescent and adult rats.

Data are presented as mean ± S.E.M. of O.D. in the dorsal raphe nucleus (A), mPFC (B), and amygdala (C) (n = 4–5) per 100×100 µm. 14–17 Days following chronic fluoxetine (12 mg/kg) treatment no differences in 5-HT1A immunostaining were found in the dorsal raphe nucleus, mPFC and amygdala. Yet, 5-HT1A receptor immunoreactivity was lower in adult compared to adolescent rats in the amygdala. ap<0.05 main age effect.

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Figure 8.

PSA-NCAM immunoreactivity in the dorsal raphe nucleus, mPFC, and amygdala of fluoxetine and methylcellulose treated adolescent and adult rats.

Data are presented as mean ± S.E.M. of the numer of immunoreactive neurons in the dorsal raphe nucleus (A), mPFC (B), and amygdala (C) (n = 4–5) per 100×100 µm. 14–17 Days following chronic fluoxetine (12 mg/kg) treatment the number of PSA-NCAM immunoreactivity was lower in adult compared to adolescent rats, but only in the dorsal raphe nucleus. In addition, we obtained a significant age x treatment interaction for PSA-NCAM immunoreactivity in the amygdala, which tended to be increased in adolescent, and decreased in adult rats. ap<0.05 main age effect; p<0.05 age x treatment interaction.

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