The dopaminergic agonist apomorphine produced dose-dependent stereotypic climbing behavior in mice housed in cages with vertical bars. This drug effect was competitively inhibited by systemic pretreatment with the centrally acting dopaminergic antagonist haloperidol but not by microwave irradiation (2.45 GHz, 20 mW/cm2, CW, 10 min) nor by systemic pretreatment with domperidone, a dopaminergic antagonist that only poorly penetrates the blood-brain barrier (BBB). Yet when mice were systemically pretreated with domperidone and then subjected to microwave irradiation (as above), the apomorphine effect was significantly reduced. Microwave irradiation also facilitated antagonism of the apomorphine effect by low and otherwise ineffective systemic pretreatment doses of haloperidol. Apomorphine-induced stereotypic climbing behavior was also reduced by domperidone administered intracerebrally, which bypassed the BBB. Exposure of intracerebral domperidone-pretreated animals to microwave irradiation failed to increase the degree of antagonism. These findings indicate that microwave irradiation can facilitate central effects of domperidone, a drug which acts mainly in the periphery. One possible explanation for these findings is that microwave irradiation alters the permeability of the BBB and increases the entry of domperidone to central sites of action.
Chronic administration of naloxone by means of miniosmotic pumps retarded the development of hypertension in young spontaneously hypertensive rats (SHRs) in a dose-related manner. Abrupt termination of naloxone treatment resulted in acceleration in the rate of the blood pressure increase, while increasing the naloxone concentration further slowed the development of hypertension in SHRs. The heart rates of SHRs undergoing chronic naloxone treatment were generally lower than those of control SHRs. Naloxone had no influence upon the mean systolic blood pressures or heart rates of normotensive Wistar-Kyoto control rats. These findings indicate that chronic naloxone treatment can alter the development of hypertension in the SHR.
We determined by radioimmunoassay concentration of dynorphin-(1-13)-like immunoreactivity in the central nervous system and pituitary gland of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). Compared to WKYs, SHRs had significantly lower levels of dynorphin-(1-13)-like immunoreactivity in the hypothalamus and pituitary gland. However, such immunoreactivity in the cerebral cortex, caudate nucleus, diencephalon, brainstem and spinal cord of SHRs and WKYs were similar.
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