Differential effects of dopaminergic drugs on open-field behavior of spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.
Brain catecholamines may play a role in the development of hypertension in the spontaneously hypertensive rat (SHR). To investigate central dopaminergic function in this strain, the effect of various dopaminergic drugs on open-field activity was assessed. In general, basal levels of ambulation were similar in SHRs and their controls, the Wistar-Kyoto rats (WKY). Exploratory rearing activity was increased in SHRs, however. Haloperidol inhibited open-field ambulation in SHRs and WKY, but higher doses were needed in the SHR. Apomorphine inhibited ambulatory activity in WKY but had virtually no effect in SHRs. Amphetamine and the dopamine uptake inhibitor GBR-12909 increased ambulation in SHRs and WKY to a similar extent. Central administration of haloperidol or sulpiride decreased ambulatory activity in WKY, but had no effect in SHRs at the doses used. SCH-23390 decreased ambulation scores both in SHRs and WKY, with the effect being slightly greater in the latter strain. In all cases exploratory rearing was affected as well by the drugs used. The large difference in base-line scores has to be taken into account when interpreting these data, however. Also, for comparison the noradrenergic drugs clonidine and desipramine were tested. Both elicited decreases in activity which were identical in SHRs and WKY. These results show that a number of dopaminergic drugs have differential effects on open-field activity of SHRs as compared to WKY. Ambulatory activity appeared more resistant to inhibition in SHRs than in WKY. The possibility that these results could reflect altered dopaminergic function in SHR involved in the development of hypertension in this strain is discussed.
van den Buuse
M
M
Rudolf Magnus Institute for Pharmacology, University of Utrecht, Medical Faculty, The Netherlands.
de Jong
W
W
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D001552:Benzazepines; D015259:Dopamine Agents; D010879:Piperazines; C043425:vanoxerine; D000661:Amphetamine; D006220:Haloperidol; D003000:Clonidine; D001058:Apomorphine; D003891:Desipramine; D004298:Dopamine