- 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.
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- INTRODUCTION
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- 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).
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- 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).
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- DISCUSSION
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- 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).
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- 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).
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- 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.
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- 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).
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- 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.
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