Francesca Ferrari

The role of dopaminergic receptors in the behavioral effects induced by lisuride in male rats

Lisuride increased the incidence of stretching and yawning (SY) as well as of penile erection (PE) and elicited stereotyped behavior (SB), aggressive behavior and mounting in male rats, depending on the dose used. SY was prevented by two dopaminergic antagonists, haloperidol and sulpiride, but not by methysergide, a serotoninergic antagonist, while PE was antagonized by all three drugs. With regard to SB, aggressive behavior and mounting, all three were suppressed by haloperidol; sulpiride, while partially antagonizing aggressiveness, failed to affect SB and mounting; methysergide did not significantly influence any of the three. This suggests that lisuride principally affects the dopaminergic system. Although further detailed studies are required to elucidate which type of the complex population of DA-receptors is involved in each kind of behavior, we suggest that SY at least is due to the activation by lisuride of presynaptic DA-receptors.

Influence of sildenafil on central dopamine-mediated behaviour in male rats

Two experiments were performed to evaluate the effects of sildenafil on spontaneous or dopamine agonist-induced behaviour in male rats. Data obtained in experiment 1 show that oral administration of the drug, at 1 mg/kg, significantly increased the occurrence of penile erections, anogenital self-grooming and homosexual mounting in grouped sexually-experienced, but not inexperienced, animals. In experiment 2, pre-treatment with sildenafil (0.5, 1 or 10 mg/kg) dose-dependently modified several behavioural signs, centrally evoked by the D2/D3 dopamine agonists, 7-OH-DPAT or B-HT 920 (both at 0.1 mg/kg), in experimentally naive male rats. While sildenafil at 1 mg/kg significantly increased the number of penile erection and stretching-yawning episodes induced by 7-OH-DPAT or B-HT 920, at 10 mg/kg it elicited low stereotyped behaviour, antagonizing stretching-yawning and sedation in 7-OH-DPAT treated rats. Discussion centres on the modulatory activity of sildenafil on central dopaminergic pathways and, possibly, on nitric oxide production.

The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat

The selective D2 antagonist eticlopride, at a dose (0.01 mg/kg, s.c.) that fails to modify the normal behavior of rats, significantly reversed all the behavioral effects exerted by the selective D2 agonist SND 919 (0.1 mg/kg, i.p.), namely, the stimulation of stretching-yawning, penile erection and sedation and the inhibition of grooming. In the copulatory test, eticlopride at the same dose did not affect animal sexual behavior but potently counteracted the reduction in mount and intromission frequency and latency to ejaculation induced by SND 919 at 0.1 mg/kg, a behavioral pattern which might possibly be proposed as an animal model for human ejaculatio praecox.

Cannabimimetic activity in rats and pigeons of HU 210, a potent antiemetic drug

Preliminary behavioral experiments in rats with the cannabinoid agonist HU 210 (12.5-100 microg/kg i.p.) showed that it has a potent cannabimimetic profile similar to that of delta9THC; the drug dose dependently depressed locomotor activity, rearing, and grooming and elicited vocalization and circling at the highest doses. In subsequent studies on pigeons, HU 210 (12.5-50 microg/kg s.c.) confirmed its sedative effects; it also afforded protection against vomiting induced by cisplatin (7.5 mg/kg i.v.) and emetine (20 mg/kg s.c.) and emetine-induced head shake.

Influence of sildenafil on copulatory behaviour in sluggish or normal ejaculator male rats: a central dopamine mediated effect?

The present study investigates the effects induced by sildenafil (1 mg/kg, p.o.) and the dopamine agonist, SND 919 (0.1 mg/kg, i.p.) on copulatory behaviour of male rats, categorized, on the basis of seven consecutive mating pre-tests, as sluggish and normal ejaculators (SE and NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and ejaculatory mechanisms of copulation. It appears that, although it induced a facilitatory effect on ejaculation of all rats, similarly to SND 919, the lowering of ejaculatory threshold was achieved by means of a reduction of mount frequency and intromission frequency in SE and NE groups, respectively. Differently from SND 919, sildenafil increased sexual arousal, diminishing post ejaculatory interval in SE animals and inter-intromission interval in both SE and NE rats. As the dopamine antagonist, (-)eticlopride (0.02 mg/kg, s.c.), significantly inhibited sildenafil-induced enhancement of sexual arousal in SE rats, it is suggested that the drug acts both peripherally and centrally.

Effects of the cannabinoid receptor agonist, HU 210, on ingestive behaviour and body weight of rats.

The effect of the synthetic cannabinoid receptor agonist, (-)11-hydroxy-Delta(8)-tetrahydrocannabinol-dymethylheptyl (HU 210), on rat body weight and eating and drinking behaviour was examined. In Experiment 1, the drug (25, 50 or 100 microg/kg), sub-chronically administered for 4 days, produced a dose- and time-dependent loss of body weight that, at the highest dose, was not regained by 7 days after the drug was stopped, and remained markedly below that of vehicle-treated animals. In Experiment 2, food and water intakes, which were evaluated in fasted rats, tested as in Experiment 1, were significantly inhibited only by the dose of 100 microgram/kg, and this effect was still present 7 days after the last injection of the drug. The possibility that the effects observed are not directly dependent on the control of appetite and might be ascribable to stress-related phenomena is discussed.

Behavioural evidence that different neurochemical mechanisms underly stretching-yawning and penile erection induced in male rats by SND 919, a new selective D2 dopamine receptor agonist

The behavioural effects induced in male Wistar rats by SND 919, a new drug reputed to have selective agonistic activity at D2 dopamine (DA) receptors, were studied. The following aspects of behaviour were considered: motor activity, stretching-yawning (SY), penile erection (PE) and stereotyped behaviour (SB). Intraperitoneal injection (IP) of the drug (0.01–20 mg/kg) induced an SY syndrome in the form of a bell-shaped dose-response curve, the effect being maximal at the dose of 0.1 mg/kg and disappearing completely at 10 mg/kg. SND 919 also potently elicited PE; this latter effect, however, was not coincident with SY induction, being maximal at 1 mg/kg and persisting at 10 and 20 mg/kg. SND 919-induced SY was potently antagonized by pretreatment not only with the D2 antagonist,l-sulpiride (20 mg/kg), but also with the α2 antagonist, yohimbine (1, 3 mg/kg), and the more selective α2 antagonist, idazoxan (1, 2 and 5 mg/kg). While sulpiride also decreased SND 919-induced PE, idazoxan at all doses and yohimbine at 1 mg/kg did not affect this behaviour. Inhibition of motor activity was induced by the D2 agonist at low doses (0.05, 0.1 mg/kg), while at high doses (1, 10 and 20 mg/kg), it was actually replaced by a form of SB characterized by downward sniffing and licking. When, for comparison, the D2 agonist, RU 24213 (0.1–20 mg/kg IP), was tested for PE, SY, motor activity and SB, it displayed a behavioural pattern very similar to that obtained with SND 919. Idazoxan (2 mg/kg), administered before RU 24213 (10 mg/kg), significantly antagonized the drug-induced SY, but not PE. The discussion centres on the specific neurochemical mechanisms presumably underlying the various forms of SND 919-induced behaviour and, in particular, PE and SY, which seem to differ, at least with respect to α2 involvement.

Modulatory activity of sildenafil on copulatory behaviour of both intact and castrated male rats

The first experiment of the present study investigates the effects induced by sildenafil (1 or 10 mg/kg po) on the copulatory behaviour of intact male rats, categorized, on the basis of seven consecutive mating pretests, as sluggish or normal ejaculators (SE or NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and the ejaculatory mechanisms of copulation, diminishing ejaculation latency in both categories and increasing copulatory efficacy in SE rats; in addition, it reduced the inter-intromission interval in both SE and NE animals and the post-ejaculatory interval only in SE animals. The second experiment, conducted on rats 3 weeks after their castration, shows that sildenafil alone (1 or 10 mg/kg) did not modify copulatory failure. However, 3 months after castration, and 24 h after the last injection of testosterone (25 microg/kg sc) given twice weekly for 4 weeks, sildenafil (1 or 10 mg/kg) ameliorated rat copulatory performance.

Potentiation of the aphrodisiac effect of N-n-propyl-norapomorphine by naloxone.

N-n-Propyl-norapomorphine (NPA), a potent dopamine (DA) receptor stimulant, in doses from 0.4 to 80 micrograms/kg i.p. produced a dose-related sexual stimulant effect characterized by recurrent episodes of penile erection (PE). The number of episodes and percentage of responding subjects were proportional to the dose. However, above the maximal effective dose, the effect decreased in a dose-related fashion until beyond 2.5 mg/kg even the natural occurrence of PE was suppressed. Morphine (5 mg/kg), as well as haloperidol (0.3 mg/kg), prevented NPA stimulation. Naloxone, which per se caused a modest increase in PE, markedly potentiated the stimulant effect of low doses of NPA, reversing the inhibitory component of higher doses. We suggest that NPA stimulation of DNA receptors causes release of opiate peptides, dampening the sexual stimulant response. The combination of DA receptor stimulants with naloxone might offer a new possibility for erection defect therapy.

Sexual attraction and copulation in male rats: effects of the dopamine agonist SND 919.

Behavioral differences towards receptive females, involving latency to the first contact, amicable behavior, genital exploration, and copulatory pattern, were seen in sexually active (A), sluggish (S), and inactive (I) male rats classified on the basis of 11 consecutive mating tests. The D2 dopamine agonist SND 919 (1 mg/kg) was intraperitoneally administered to the three groups 25 min before a 12th test; the drug stimulated the copulatory behavior of A and S but not of I rats in which it diminished genital exploration and amicable behavior. In a 13th test, conducted 1 week later, 31% of I initiated mating, 16% of them reaching ejaculation. The stimulant effect of SND 919 on copulation in A rats was confirmed in further experiments where it was injected at 0.1 mg/kg, a dose selective for the D2 autoreceptors.