mise à jour du
16 novembre 2005
Pharmacological Research
1985; 17; 6; 557-563
Sexual excitement and stretching
and yawning induced by b-ht 920
Francesca Ferrari
Institute of Pharmacology, University of Modena, Italy
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren


Abstract The azepine derivative B-HT 920, a putative agonist at dopamine (DA) autoreceptors, injected IP in adult male rats, induced numerous penile erections (PE) and stretching and yawning (SY), considered typical signs of central DA receptor stimulation, without eliciting stereotyped behaviour (SB). Both signs induced by B-HT 920 were dose related and significantly enhanced with respect to controls from 10 to 1,000 µg/Kg. Pretreatment with the neuroleptics haloperidol (0.025, 0.5 and 1 mg/Kg IP), sulpiride (20 and 40 mg/Kg) and alpha2-antagonist yohimbine (1 and 3 mg/Kg IP) antagonized the behavioural effect of B-HT 920 whereas the 1-antagonist prazosin (1 mg/Kg IP) had no effect on the response. The impressive activity of B-HT 920 in producing SY and PE, along with its inability to evoke SB, supports the role of DA autoreceptors in the regulation of SY and sexual behaviour.
Previous studies showed that dopamine (DA) receptor stimulants, such as apomorphine, N-n-propylnorapomorphine (NPA), bromocriptine and lisuride have in common the ability to elicit repeated penile erections (PE) and stretching and yawning (SY) in rats (Baraldi and Benassi-Benelli 1975, Mogiinicka and Klimek 1977; Baggio and Ferrari 1983) besides stereotyped behavior (SB), classically considered the typical expression of DA receptor stimulation (Randrup and Munkvad 1968). Generally, DA agonists have biphasic activity, inducing PE and SY at low doses and losing this capacity at doses large enough to produce considerable SB (Ferrari and Baggio 1982a; Baggio and Ferrari 1983) suggesting that different classes of receptors underlie PE and SY on the one hand, and SB, on the other (Baggio and Ferrari 1983).
However, until now, the DA agonists tested for PE, have been reported as acting on both pre- and post-synaptic DA receptors (Martin et al. 1982), thus rendering any hypothesis open to dispute. In order further to clarify the role of DA and possibly other receptors in controlling erection mectianisms besides SY, which would appear to reflect autoreceptor stimulation (Baggio and Ferrari 1983, Mogiinicka et al. 1984, Stàhle and Ungerstedt 1984), we studied the effect on the parameters considered of B-HT 920, a drug generally considered a DA autoreceptor agonist (Andén et al. 1982) but also active on alpha2 adrenoceptors (Van Meel et al. 1981).
In agreement with the data already published (Andén et al. 1982, Grabowska-Andén and Andén 1983) B-HT 920 failed to evoke SB. It was, however, seen to be an impressive stimulant of SY and PE. Pretreatment with either haloperidol or sulpiride clearly inhibited the effects induced by B-HT 920, thus confirming the hypothesis that a dopaminergic mechanism is involved. B-HT 920, apart from being a selective DA autoreceptor agonist (Andén et al. 1982) is also thought to be a potent alpha2-adrenoceptor agonist (Van Meel et al. 1981).
Yohimbine, generally considered to produce a specific blockade of alpha2-receptors (Shepperson et al. 1981), unexpectedly behaved similarly to the two dopaminergic antagonists, inhibiting both the PE and SY induced by B-HT 920. This was the more unexpected as yohimbine was long used as an aphrodisiac in the treatment of impotence (Margolis et al. 1967). The two doses of yohimbine used (1 and 3 mg/Kg IP) are in the range reported selectively to antagonize alpha2-adrenoceptors (Andén et al. 1982).
Our results lead to three possible considerations: that typical dopaminergic agonists do not, after all, act exclusively on DA receptors, or that the antagonists used do not, after all, act so selectively as is supposed, or, finally, that there is, as has been suggested, some interconnection between the adrenergic and dopaminergic systems (Andén and Grabowska 1976). While it is well known that haloperidol may act non-specifically, there have been scant reports of any interference by yohimbine with other than alpha2-adrenergic receptors (Golberg and Robertson 1983), at any rate, at the dose used by us.
However, in accordance with Goldberg and Robertson (1983), although blockade of alpah2-adrenoceptors is, to date, the most easily demonstrable of yohimbine's effects, activity on other systems cannot be excluded. In particular, it has been reported that yohimbine (0.1 to 3 mg/Kg) increased DA turnover in the striatum of rats, suggesting blockade of D2-receptors (Scatton et al. 1980).
Since, in the male rat, drug-induced PE in the absence of females in estrus is generally an indicator of sexual hyperstimulation (viz. the results obtained in the complete copulatory test (Ahlenius et al. 1980, Ferrari and Baggio 1982b and Ferrari et al.l984), and clinical findings (Lal 1981)), the present results would appear to point to the need for a re-appraisal of the neurochemical pathways underlying the erection mechanisms and for the identification of drugs that may be useful in treating certain forms of impotence in man.