Among the therapeutic treatments for attention deficit with hyperactivity disorder (ADHD), the psycho-stimulant methylphenidate (MP), represents the classic treatment while atomoxetine (ATO), a selective noradrenaline (NA) reuptake inhibitor, has been proposed successfully as an alternative to stimulant treatment. Spontaneous hypertensive (SH) rats, because they show several behavioural abnormalities (hyperactivity, hype-reactivity to stress and cognition deficit) have been proposed as an animal model of ADHD. The aim of this study, performed in male and female adolescent SH rats, was to assess the consequences of a 14 day treatment with MP, 1 mg/kg i.p. or ATO, 3 mg/kg i.p. or saline, twice a day on: i), the extracellular concentration of dopamine (DA) and NA in the PFC through the “in vivo” microdialysis method; ii) the spontaneous behavioural activity. We observed that neither MP nor ATO treatment changed the basal extracellular concentration (output) of NA or of DA in the PFC. We also observed that a challenge dose of MP (1 mg/kg i.p.) increased maximally NA output by 350 % and by 150 % and DA output by 158 % and 178 % in saline and MP male SH treated rats respectively. Moreover, a challenge dose of ATO (3 mg/kg i.p.) increased maximally NA output by 377 % and by 325 % and DA output by 287 % and 245 % in saline and ATO male SH treated rats respectively. Moreover we observed that a challenge dose of MP (1 mg/kg i.p.) increased maximally NA output by 210 % and by 200 % and DA output by 154 % and 144 % in saline and MP female SH treated rats respectively whereas a challenge dose of ATO (3 mg/kg i.p.) increased maximally NA output by 341 % and by 279 % and DA output by 192 % and 324 % in saline and ATO female SH treated rats respectively. Furthermore the sub-chronic treatment with MP or ATO determined a reduction of the locomotor activity in male but not in female SHR. Our most interesting results show that: i) acute ATO increased DA transmission much more than MP although they produced a similar effect on NA transmission in the PFC of SH control rats; ii) PFC basal NA and DA output was not affected by MP or ATO treatment in both male and female SHR; iii) MP treatment determines a strong tolerance to its challenge effect on NA transmission in the PFC of males but not female SHR. In summary our results suggest that the sub-chronic treatment with MP or ATX determine different and gender specific neurotransmission changes in PFC and gender specific spontaneous locomotor activity reduction.
52) Carboni E., Ibba M., Schirru C., Sadile A. (2009). BEHAVIORAL AND NEUROCHEMICAL CHANGES INDUCED BY METHYLPHENIDATE OR ATOMOXETINE SUB-CHRONIC TREATMENT IN ADOLESCENT SPONTANEOUS HYPERTENSIVE RATS (SHR) ARE GENDER SPECIFIC
CARBONI, EZIO;
2009-01-01
Abstract
Among the therapeutic treatments for attention deficit with hyperactivity disorder (ADHD), the psycho-stimulant methylphenidate (MP), represents the classic treatment while atomoxetine (ATO), a selective noradrenaline (NA) reuptake inhibitor, has been proposed successfully as an alternative to stimulant treatment. Spontaneous hypertensive (SH) rats, because they show several behavioural abnormalities (hyperactivity, hype-reactivity to stress and cognition deficit) have been proposed as an animal model of ADHD. The aim of this study, performed in male and female adolescent SH rats, was to assess the consequences of a 14 day treatment with MP, 1 mg/kg i.p. or ATO, 3 mg/kg i.p. or saline, twice a day on: i), the extracellular concentration of dopamine (DA) and NA in the PFC through the “in vivo” microdialysis method; ii) the spontaneous behavioural activity. We observed that neither MP nor ATO treatment changed the basal extracellular concentration (output) of NA or of DA in the PFC. We also observed that a challenge dose of MP (1 mg/kg i.p.) increased maximally NA output by 350 % and by 150 % and DA output by 158 % and 178 % in saline and MP male SH treated rats respectively. Moreover, a challenge dose of ATO (3 mg/kg i.p.) increased maximally NA output by 377 % and by 325 % and DA output by 287 % and 245 % in saline and ATO male SH treated rats respectively. Moreover we observed that a challenge dose of MP (1 mg/kg i.p.) increased maximally NA output by 210 % and by 200 % and DA output by 154 % and 144 % in saline and MP female SH treated rats respectively whereas a challenge dose of ATO (3 mg/kg i.p.) increased maximally NA output by 341 % and by 279 % and DA output by 192 % and 324 % in saline and ATO female SH treated rats respectively. Furthermore the sub-chronic treatment with MP or ATO determined a reduction of the locomotor activity in male but not in female SHR. Our most interesting results show that: i) acute ATO increased DA transmission much more than MP although they produced a similar effect on NA transmission in the PFC of SH control rats; ii) PFC basal NA and DA output was not affected by MP or ATO treatment in both male and female SHR; iii) MP treatment determines a strong tolerance to its challenge effect on NA transmission in the PFC of males but not female SHR. In summary our results suggest that the sub-chronic treatment with MP or ATX determine different and gender specific neurotransmission changes in PFC and gender specific spontaneous locomotor activity reduction.
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