The contrasting effects of repeated methylphenidate treatment in methylphenidate self-administration and reinstatement in Wistar and SHR, and the increased susceptibility of the Wistar rat strain to the reinforcing effects of methylphenidate indicate that "normal" individuals are more likely to develop psychological dependence to the drug and experience relapse. Meanwhile, the clinical use of methylphenidate may not produce drug dependence or relapse in ADHD patients.

We previously reported that oroxylin A, a γ-aminobutyric acid A (GABAA) receptor antagonist, ameliorates drugs-induced memory impairments. We synthesized several oroxylin A derivatives in efforts to find a substance that has pro-cognitive effects as well as improves sensorimotor gating. The aim of the present study is to investigate the effect of a novel oroxylin A derivative, 5,7-dihydroxy-6-methoxy-2(4-phenoxyphenyl)-4H-chromene-4-one (DMPC), on pharmacological models of schizophrenia, which exhibit memory impairment and sensorimotor gating deficit. Memory impairment was induced by scopolamine, a muscarinic receptor antagonist, or MK-801, an N-methyl-D-aspartate receptor antagonist. Sensorimotor gating deficits were induced by MK-801 and measured by prepulse inhibition (PPI) of the acoustic startle response task. DMPC treatment (20 mg/kg) significantly attenuated scopolamine- or MK-801-induced memory impairment and it even enhanced cognitive performance of normal animals. Furthermore, DMPC significantly ameliorated MK-801-induced PPI deficits in the acoustic startle response task. In an in vitro study, DMPC (20 μM) inhibited intracellular Cl(-) influx induced by muscimol, a selective GABAA receptor agonist. These results suggest that DMPC would be a potential candidate for alleviating cognitive dysfunction and sensorimotor gating deficits in schizophrenia, and that its effects may be mediated, in part, via blockade of the GABAergic neurotransmitter system.

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Abstract"ttention-deficit/hyperactivity disorder "DHD is the most common neurodevelopmental disorder of childhood characterized by the three core symptoms of hyperactivity, impulsiveness, and sustained inattention. While the etiology of "DHD remains unknown, several studies suggest "DHD pathophysiology to involve frontal network abnormality and dysregulation of catecholaminergic and dopaminergic functions. Stimulants, which are structurally similar to endogenous catecholamines, are the most commonly prescribed drugs for treatment of "DHD, but are classified as Schedule II based on the Controlled Substances "ct due to high likelihood for diversion and abuse. Non-stimulant medications, as well as antidepressants, have also been used in "DHD treatment but have been found to be inferior to stimulant interventions and to cause intolerable side effects. The search for safer yet effective "DHD treatments led to a growing interest in natural medicines and a host of other complementary and alternative treatments for "DHD. While the use of these therapies is well documented, not much is known about their safety and efficacy. In this chapter, we describe current evidence-based complementary and alternative therapies for "DHD, focusing on nutritional and botanical agents, and provide details on the performance of these agents in clinical trials. Here, we discuss the rationale for the use of natural products for "DHD, mention the potential mechanisms of action of these treatments, and highlight safety and efficacy issues associated with the use of these treatments. In conclusion, we give an exhaustive update on the use of nutritional and botanical medicines as complementary and alternative "DHD therapies for "DHD, which