Gen. Pharmac. Vol. 23, No. 4, pp. 671q575, 1992 Printed in Great Britain.All rights reserved

0306-3623/92$5.00+ 0.00 Copyright © 1992PergamonPress Ltd

OPPOSITE INFLUENCES OF DOPAMINERGIC RECEPTOR SUBTYPES ON PENILE ERECTION MOHAMMAD-REZA ZARRINDAST,* SHAHROKHSHOKRAVI and MORTEZASAMIN1 Department of Pharmacology, Medical Faculty, University of Tehran, P.O. Box 13145-784Tehran, Iran

(Received I0 December 1991) Abstract--l. Mixed D-I/D-2 dopamine agonist apomorphine induced a penile erection (PE) in rats in a biphasic manner. 2. The response was decreased with increasing doses of the drug. 3. The maximum effect was obtained by 0.1 mg/kg of apomorphine. 4. In animals pretreated with D-I antagonist SCH 23390, high doses of apomorphine showed higher PE response, while D-2 antagonist sulpiride pretreatment decreased the response of the low doses of the drug. 5. The inhibitory effect of sulpiride was dose-dependent. 6. The D-2 agonists bromocriptine or quinpirole induced a dose-dependent PE. 7. The effects of both drugs were decreased by sulpiride or SKF 38393 pretreatment. 8. Cholinergic drugs physostigrnine and neostigmine did not induce PE, but antimuscarinic agent atropine decreased the effects of apomorphine, bromocriptine or quinpirole. 9. It is concluded that D-2 dopamine receptor stimulation may induce PE, while D-I activation elicit an opposite effect. 10. However, cholinergic stimulation is not able to induce PE, cholinergic inhibition may decrease the PE induced by dopaminergic agents.

INTRODUCTION

Procedure Rats were placed individually in a glass cylinder (25 cm wide, 25 cm high) and a mirror was arranged in an oblique position under the cyclinder to make observation possible. Animals were allowed to habituate for 30 rain before drug injection. PE episodes were counted by direct observation after drug administration. The results were recorded and expressed as number of PE episodes for a period of 60 min. Analysis of variance (ANOVA) followed by Student's t-test were used to evaluate significance in the results obtained.

The existence of two dopamine receptor subtypes in the brain which have been named D-I and D-2 is well established. The D-I subtype is defined as that positively linked to adenylate cyclase while the D-2 sites is negatively coupled or uncoupled to this enzyme (Kebabian and Caln¢, 1979; Stoof and Kebabian, 1984). It was previously shown that yawning and penile erections (PE) are elicited by many dopamine agonists (Mogilinka and Klimek, 1977; Benassi-Benelli et al., 1979). The yawning and PE syndromes are claimed to be the consequence of stimulation of D-2 dopamine receptors (Gower et al., 1984; Zarrindast and Poursoltan, 1989). The involvement of serotonergic mechanism in the PE have also been suggested by some investigators (Baraldi et al., 1977; Berendsen et al., 1990). The PE induced by the dopamine agonist apomorphine has been shown to be antagonised by the serotonergic antagonists methergoline and methysergide (Gower et al., 1984). However, the involvement of different 5-HT receptors in PE have been investigated, the possible role of different dopamine receptor subtypes has not been clarified. In the present work, the effect of D-I and D-2 dopamine receptors on the PE induced by dopaminergic agents have been investigated. MATERIALS AND METHODS Animals Male albino rats weighing 250-300 g were used in these experiments. The animals were housed in groups of 10, under controlled 12 hr light/dark cycles. The animals were allowed ad libitum access to food and water, except during the time of experiments.

*To whom all correspondence should be addressed.

Drugs The following drugs were used: apomorphine hydrochloride (MacFarlan Smith Ltd, England), bromocriptine (Sandoz, Switzerland), SKF 38393 (i-phenyl-7,8-dihydroxy2,3,4,5-tetrahydro-IH-3-benzazepine hydrochloride; R. B. Inc. Wayland, U.S.A.), quinpirole hydrochloride (Eli Lilly, U.S.A.), SCH 23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro3-methyl-5-phenyl-lH-3-bezazepine-7-olmaleate; Schering, Italy], sulpiride (Delagrange, France), atropine sulphate (Merck, Fed. Rep. Germany), physostigmine salicylate (Sigma, England), neostigmine methylsulphate (amp., Waldemar-Weiner, Fed. Rep. Germany) and pilocarpine hydrochloride (Sigma, England). Bromocriprine was dissolved in saline by the use of crystalline tartaric acid and a few drops of alcohol. Sulpiride was dissolved in a drop of acetic acid and water. The other drugs were dissolved in saline. The drugs were prepared immediately before use and were injected in a volume of 10ml/kg except for apomorphine which was injected in a volume of 2 ml/kg. RESULTS Induction o f P E by apomorphine in presence or absence o f dopamine antagonists in rats Subcutaneous (s.c.) administration of different doses (0.1, 0.3 and 0.5 mg/kg) of apomorphine induced a biphasic PE in the rats. Pretreatment of animals intraperitoneally (i.p.) with sulpiride (12.5 mg/kg, 90 rain)

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Fig. 1. Animals were treated s.c. with different doses of apomorphine ( 0 : 0.1, 0.3 and 0.5mg/kg) alone or in combination with i.p. administration of either SCH 23390 ( , : 0.05 mg/kg) 30 rain or sulpiride (A: 12.5 mg/kg) 90 rain before apomorphine injection. Frequency of PE was recorded during 60 min after drug administration. Each point is the mean +SEM of at least 7 rats. *P

Opposite influences of dopaminergic receptor subtypes on penile erection.

1. Mixed D-1/D-2 dopamine agonist apomorphine induced a penile erection (PE) in rats in a biphasic manner. 2. The response was decreased with increasi...
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