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General pharmacological studies were performed on (6)-gingerol and (6)-shogaol which are the pungent constituents of ginger (Zingiber officinale Roscoe). Intravenous (i.v.) administration of (6)-gingerol (at 1.75-3.5 mg/kg) or (6)-shogaol (at 1.75-3.5 mg/kg) and oral administration of them (at 70-140 mg/kg) produced an inhibition of spontaneous motor activity, an antipyretic and analgesic effects, prolonged hexobarbital-induced sleeping time, and these effects of (6)-shogaol were mostly more intensive than that of (6)-gingerol. (6)-Shogaol showed an intense antitussive effect in comparison with dihydrocodeine phosphate. In the electro-encephalogram of cortex, the low amplitude fast wave pattern was observed for 5 min after i.v. administration of (6)-shogaol, and then changed to the drowsy pattern, which was restored after 60 min. In the gastro-intestinal system, (6)-shogaol intensively inhibited the traverse of charcoal meal through the intestine in contrast with (6)-gingerol after i.v. administration of 3.5 mg/kg, but (6)-shogaol facilitated such an intestinal function after oral administration of 35 mg/kg. Both (6)-shogaol and (6)-gingerol suppressed gastric contraction in situ, and the suppression by the former was more intensive than that by the latter. In the cardiovascular system, both (6)-shogaol and (6)-gingerol produced depressor response at lower doses on the blood pressure. At high doses, both drugs produced three phase pattern.

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Glucocorticoid hormones are important in the maintenance of many brain functions. Although their receptors are distributed abundantly throughout the brain, including the prefrontal cortex (PFC), it is not clear how glucocorticoid functions, particularly with regard to cognitive processing in the PFC. There is evidence of PFC cognitive deficits such as working memory impairment in several stressrelated neuropsychiatric disorders, including depression, schizophrenia, and Parkinson's disease. Disruption of the hypothalamopituitary-adrenal (HPA) system, which is characterized by attenuated glucocorticoid negative feedback, is also observed. In rats, chronic stress induces working memory impairment as a result of decreased dopaminergic transmission in the PFC. These chronically stressed rats also show HPA disruption; this is caused in part by a reduced glucocorticoid response in the PFC. These findings implicate reduced glucocorticoid actions in working memory impairment. In the present study, we examined the effects of the suppression of endogenous glucocorticoids by adrenalectomy (ADX) on working memory in rats and explored the involvement of PFC dopaminergic activities in memory. The ADX impaired working memory, decreased dopamine release, and upregulated D 1 receptors in the PFC. These dysfunctions were prevented by corticosterone replacement that reproduced normal physiological plasma levels, indicating that suppression of glucocorticoids causes these dysfunctions. Moreover, the ADX-induced working memory impairment was ameliorated by intra-PFC infusions of a D 1 receptor agonist, SKF 81297. Thus, suppression of glucocorticoids impaired working memory through a D 1 receptormediated hypodopaminergic mechanism in the PFC. This finding indicates that endogenous glucocorticoids are essential for maintaining PFC cognitive function and suggests that HPA disruption contributes to PFC cognitive deficits.

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