Differences in Methylphenidate Dose Response between Periadolescent and Adult Rats in the Familiar Arena-Novel Alcove Task

Abstract

Methylphenidate is a psychostimulant widely used in the treatment of attention deficit hyperactivity disorder. In this study, the effects of two nonstereotypy-inducing doses of methylphenidate (2.5 and 5.0 mg/kg s.c.) were examined in periadolescent [postnatal days (P) 35 and 42] and young adult (P70), male Long-Evans rats using a three-period locomotor activity paradigm that affords inferences about exploration, habituation, and attention to a novel stimulus (an "alcove") in a familiar environment in a single test session. In the first test period, P35 and P42 rats were more active than P70 rats, and methylphenidate increased locomotion in a dose-related manner. The introduction of a novel spatial stimulus in the third test period revealed a significant interaction of dose and age such that P70 rats exhibited dose-related increases in distance traveled, but P35 rats did not. Furthermore, methylphenidate dose-relatedly disrupted the rats' tendency to spend increasing amounts of time in the alcove across the test period at P70 but not at P35. Brain and serum methylphenidate concentrations were significantly lower at P35 than at P70, with intermediate levels at P42. Developmental differences in dopaminergic neurochemistry were also observed, including increased dopamine content in the caudate-putamen, nucleus accumbens, and frontal cortex and decreased densities of D 1 -like receptors in the frontal cortex in P70 than in P42 rats. These results raise the possibility that children and adults may respond differently when treated with this drug, particularly in situations involving response to novelty and that these effects involve developmental differences in pharmacokinetics and dopaminergic neurochemistry.

A novel use of combined tyrosine hydroxylase and silver nucleolar staining to determine the effects of a unilateral intrastriatal 6-hydroxydopamine lesion in the substantia nigra: A stereological study

“…2). The dopamine levels measured in the unlesioned hemispheres were comparable to those found in previous studies (Davis et al, 2010; Kilts et al, 1981; Levant et al, 2011; Widerlöv et al, 1982). …”

Postnatal Nitric Oxide Inhibition Modifies Neurotensin Effect on ATPase Activity

“…Habituation is a simple form of learning which has been used to study behavioral consequences resulting from brain lesions or pharmacological manipulations. Present results showed that the number of crosses in the open field task for control animals is lower in a second and third period of exposure, in agreement with data from the literature [23,24]. After the treatment with L-NAME a dose dependent increase in the number of crosses and rearing was recorded at the first period in juvenile rats, which may be associated with positive symptoms of the schizophrenia [25].…”

Impaired executive functions in experimental model of temporal lobe epilepsy

“…hyperactivity was observed over time in a familiar environment with neutral context (open field) and in a threatening environment. it is interesting to mention that the locomotor hyperactivity in children with ADhD as well as animal model of ADhD (e.g spontaneous hypertensive rats) tend to be less pronounced in novel environments than in familiar ones 14 , and for that reason the test was repeated 3 times with 7 days apart. in addition, our results are in agreement with Kubova et al 15 , which reported increased locomotor activity in rats submitted to kainic acid (KA) model at PN25 (25 day of life).…”