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•Age and sex differences exist in novelty seeking, reactivity, and sucrose preferences•Sucrose preferences in juveniles predict cocaine intake; novelty does not•Number of days to stable intake predicts the total amount of cocaine administered

Although stimulants are widely prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), their calming effects are not easily understood. One hypothesis derived from preclinical studies is that stimulants exert "rate-dependent" effects that are inversely related in magnitude and direction to the baseline rate of activity or distraction. Previously, compelling support for this hypothesis has been lacking. We provide preliminary evidence that methylphenidate exerts rate-dependent behavioral effects in children with ADHD. Activity and attention were quantified in children with ADHD tested on placebo and different doses of methylphenidate using objective measures. Higher doses altered activity and attentiveness in a rate-dependent manner after correction for regression-to-the-mean artifacts. These findings illustrate a clear inverse association between symptom severity and degree of therapeutic response that is crucial for our understanding of stimulant effects and effective clinical treatment of ADHD.

The unique maturational period of adolescence is replete with numerous changes in anatomy and function that may yield clues as to why drug abuse emerges at this stage. The behavioral effects of amphetamine are diminished during periadolescence (35 days) relative to younger (21 days) and older (>60 days) rats, prompting us to examine amphetamine effects on neuronal activation with the immediate early gene, c‐fos.Amphetamine (1 and 5 mg/kg, i.p.) increased c‐fos immunoreactivity in rats 21, 35, and 60 days of age in a dose‐dependent manner. When expressed as a percentage of vehicle for each age, amphetamine‐induced effects on c‐fosimmunoreactivity were higher at 21 days of age compared with the effects at 35 and 60 days of age in the nucleus accumbens core and shell, striatum, and prefrontal cortex. These data provide a possible reason as to why stimulants produce dysphoria in children, before transitioning to euphoria during adolescence. Implications of these results are discussed for stimulant use in a pediatric population and the development of drug abuse. Synapse 41:345–350, 2001. © 2001 Wiley‐Liss, Inc.

Behavior in the elevated plus maze was correlated with hemispheric asymmetries in neurotransmitter content in limbic brain regions assayed with HPLC-EC in adult rats. A strong (r = 0.86, p<0.003) correlation exists between increased anxiety (more time spent in the closed arm) and the lateralization of serotonin in the amygdala. Greater serotonin in the right versus left amygdala relates to greater anxiety. In addition, increased dopamine in right prefrontal cortex is strongly correlated with anxiety (r = 0.84, p<0.01). No such correlations were observed for accumbens, hippocampus, or striatum. These data support the hypothesis that the right hemisphere is involved in emotional states: increased serotonin in the right amygdala is related to anxiety, while cortical dopamine may be associated with attention to the environment.

The effects of apomorphine (0.05, 0.1, and 1.0 mg/kg, s.c.) on the extracellular levels of dopamine and the dopamine metabolite 3, 4‐dihydroxyphenylacetic acid were studied through the use of in vivo microdialysis in the neostriatum of developing and adult rats. Fifteen‐minute samples were collected from urethane‐anesthetized rats 5, 10–11, 21–22, and 35–36 days old and adults and quantified by HPLC with electrochemical detection. Apomorphine attenuated extracellular levels of dopamine in all age groups, suggesting that the dopamine autoreceptor modulating release in the neostriatum is functional by 5 days of age. A dose‐response effect of apomorphine on extracellular dopamine was observed in all age groups except at 10–11 days of age. Extracellular levels of 3, 4‐dihydroxyphenylacetic acid were also significantly decreased in all age groups, consistent with the hypothesis that synthesis‐modulating dopamine autoreceptors in the neostriatum are functional by 5 days of age. Apomorphine had a significantly greater effect on extracellular 3, 4‐dihydrpxyphenylacetic acid levels at the 0.05 and 0.1 mg/kg doses in the 5‐ and 10–11‐day‐old age groups compared with the other ages. Absolute levels of extracellular dopamine were significantly attenuated at 5 days of age compared with the other ages, and absolute levels of extracellular 3, 4‐dihydroxyphenylacetic acid monotonically increased with age.

The effects of apomorphine (0.05, 0.1, and 1.0 mg/kg, s.c.) on K+-evoked dopamine release were studied through the use of in vivo microdialysis in the neostriatum of developing and adult rats. Fifteen-minute samples were collected from urethane-anesthetized rats 5, 10–11, 21–22, 35–36 days of age, and adults, and quantified by high performance liquid chromatography with electrochemical detection. Apomorphine attenuated K+-evoked dopamine release in all age groups, suggesting that the dopamine autoreceptor modulating release in the neostriatum is functional by 5 days of age. A dose-response effect of apomorphine was observed in all age groups except at 5 and 10 days of age. Absolute levels of extracellular dopamine were significantly lower at 5 and 10 days of age compared with the other ages, and the effectiveness of a high-K+ artificial cerebrospinal fluid to evoke dopamine release increased with age.

No abstract.

DENSITY of dopamine D1and D2family receptors was assessed using autoradiography in male and female rats from 25 to 120 days of age, focusing on transitions through puberty into full adulthood. Males had greater overproduction (approximately 4.6-fold) and elimination of striatal D1and D2receptors than females, though their adult densities were very similar. Males had more extensive overproduction of D1receptors in nucleus accumbens and sustained a greater density into adulthood (57.8 ± 21.2). These results have implications for understanding gender differences in the prevalence of clinical disorders associated with dopamine.

No abstract.