Microwave facilitation of domperidone antagonism of apomorphine-induced stereotypic climbing in mice.
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.
D000818:Animals; D001058:Apomorphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008872:Microwaves; D013239:Stereotyped Behavior / Q000187:drug effects* / Q000528:radiation effects
D004294:Domperidone; D006220:Haloperidol; D001058:Apomorphine