Biomedical subjects
Publications and source records attributed to M Collu.
B-HT 920, a selective DA autoreceptor agonist, reduced motor activity in rats. Chronic, but not acute, treatment with imipramine (IMI) reversed this effect. The mechanism by which chronic IMI reverses the B-HT 920 effect is discussed.
The effect of chronic treatment with antidepressants (ADs) on the behavioral responses to LY 171555, a selective D2 receptor agonist, SKF 38393, a selective D1 receptor agonist, and B-HT 920, a selective DA autoreceptor agonist, was studied in rats. In normal rats small, intermediate and high doses of LY 171555 produced hypomotility, hyperactivity and stereotypies, respectively. Chronic but not acute pretreatment with imipramine (IMI) greatly potentiated the motor stimulant effect of LY 171555, but failed to modify its stereotypic and sedative effect. The potentiation of the motor stimulant effect of LY 171555 was observed also after chronic, but not acute, treatment with desmethylimipramine (DMI), mianserin (MIA) or repeated electroconvulsive shock (ECS). Chronic treatment with IMI failed to modify the effect of SKF 38393 (motor stimulation, grooming and penile erection), but reversed the sedative effect of B-HT 920 into a motor stimulant response. The motor stimulant response to LY 171555 in IMI-pretreated animals was suppressed by L-sulpiride, a D2 antagonist, and by a combination of reserpine with alpha-methyltyrosine (alpha-MT), but it was only partially antagonized by high doses of SCH 23390, a selective D1 antagonist. The results indicate that chronic treatment with ADs potentiates the behavioural responses mediated by the stimulation of postsynaptic D2 receptors in the mesolimbic system and suggest that this behavioural supersensitivity is due to enhanced neurotransmission at the D1 receptor level.
L-Sulpiride is a dopamine (DA)-receptor blocker that acts as an antidepressant at low doses. We have reviewed evidence suggesting that the antidepressant effect of L-sulpiride may depend on the activation of DA transmission secondary to the blockade of DA autoreceptors.
The effect of the intracerebroventricular (ICV) injection of the oxytocin antagonist d(CH2)5Tyr(Me)-Orn8-vasotocin on the stimulation of copulatory behavior induced by the dopamine (DA) agonist apomorphine was studied in male rats. Apomorphine (80 micrograms/kg SC) given 5 min before mating tests decreased intromission frequency and ejaculation latency in experienced male rats. Such effects were abolished and reversed by pretreatment with 50 and 1000 ng of the oxytocin antagonist given ICV 5 min before apomorphine. The peptide per se markedly increased intromission and ejaculation latency and abolished ejaculation in control rats. The results suggest that brain oxytocin is implicated in the expression of sexual behavior, and apomorphine might improve male copulatory behavior by releasing oxytocin in brain.
The effect of an intracerebroventricular (i.c.v.) injection of the oxytocin antagonist, d(CH2)5Tyr(Me)-Orn8-vasotocin, on the copulatory behaviour of vigorous male rats in the presence of females in estrus was studied. The peptide (2.5, 25 and 50 ng, 15 min before mating tests) decreased the number of mounts and intromissions, and abolished ejaculation almost completely at all doses tested. The peptide failed to significantly influence motor activity at the doses used. The results support the hypothesis that central oxytocin plays a physiological role in the expression of copulatory behaviour.
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REM sleep deprivation induced by means of the platform technique (72 h) was followed by a period of latency to sleep characterized by a marked excitement in rats. The administration of naloxone at the end of the REM deprivation period reduced this latency to sleep while morphine, beta-endorphin and DADLE prolonged it. The dopamine D1 receptor antagonist SCH 23390 was extremely potent (0.003 mg/kg) to reduce the latency to sleep and the excitement while the D1 agonist SKF 38393 induced an opposite effect. The dopamine D2 receptor antagonist L-sulpiride was inactive up to a dose of 25 mg/kg. These data suggest that hyperactivity of the opioid and dopamine systems (specifically mediated through D1 receptors) is involved in such behaviour.
The subtype of dopamine (DA) receptors mediating the yawning response to DA agonists was determined in rats. Yawning was elicited both by the mixed D1-D2 agonist apomorphine and by the specific D2 agonist LY 171555, but not by the selective D1 agonist SKF 38393. Both apomorphine- and LY 171555-induced yawning were antagonized not only by the selective D2 antagonist sulpiride but, unexpectedly, also by the selective D1 antagonist SCH 23390. The results suggest that DA receptors mediating the yawning response are of the D2 type, and that these receptors are connected with D1 receptors in such a way that the blockade of the latter results in the functional inactivation of the former.
The intracerebroventricular administration of ACTH1-24 (3-5 micrograms/rat) produced a behavioural syndrome characterized by recurrent episodes of penile erection and yawning in rats. Hypophysectomy prevented ACTH1-24-induced yawning and penile erection. These results suggest that pituitary has a "trophic" action not only on peripheral target organs but also on structures in brain controlling specific behavioural responses.
Yawning was induced in rats by the (+) enantiomer of 3PPP, while (-)-3PPP was inactive. Yawning was present 24, but not 1, 6 and 12 h after reserpine treatment. The (+)-3PPP-induced yawning was antagonized by haloperidol and sulpiride but not by domperidone. Reserpine-induced yawning was antagonized by sulpiride and by alpha-methyltyrosine suggesting that this behavior may be induced by endogenously released dopamine. Reserpine-pretreatment potentiated (+)-3PPP-induced yawning. The results argue against the view that yawning is the behavioural correlate of autoreceptor-mediated inhibition of DA transmission, and suggest that this behaviour is due to the stimulation of a special population of central postsynaptic DA receptors.
In unanesthetized rats the intravenous administration of low doses of ethanol (0.125-0.5 g/kg) produced a dose-dependent increase (30-80%) in the firing rate of dopaminergic (DA) neurons in the Ventral Tegmental Area (VTA). In agreement with previous observations, a dose range between 0.5 and 2 g/mg of ethanol was needed to produce comparable stimulant responses in DA neurons of the Substantia Nigra Pars Compacta. However, in anesthetized rats, doses of ethanol up to 1 g/kg failed to activate VTA-DA neurons. The high sensitivity of VTA-DA neurons to ethanol activation suggests that they might be involved in the reinforcing properties of the drug.
SCH 23390, a rather selective D1 receptor blocker, activates the firing rate of dopamine (DA) neurons in the substantia nigra (SN-DA neurons) in rats, similarly to haloperidol (a D1-D2 receptor antagonist) and sulpiride (a selective D2 receptor blocker). These neuroleptics produce no additional increase over the maximal activation produced by SCH 23390. Unlike haloperidol or sulpiride, SCH 23390 fails to prevent the inhibition by apomorphine of SN-DA neurons, a DA autoreceptor-mediated effect. It is suggested that the doses of SCH 23390 that stimulate DA neurons block D2 in addition to D1 receptors, or that D1 blockade results in the functional inactivation of a specific population of D2 receptors as well. The failure of SCH 23390 to block the apomorphine effect indicates that DA autoreceptors can be pharmacologically differentiated form postsynaptic DA receptors.
The effect of SCH 23390, a selective blocker of D-1 receptors, on apomorphine-induced behavioural and EEG changes was studied in rats. In control rats, a low dose of apomorphine (50 micrograms/kg s.c.) produced sedation associated with EEG synchronization. A high dose of apomorphine (1 mg/kg s.c.) produced stereotypy associated with EEG desynchronization. At the dose of 1 mg/kg i.p., SCH 23390 decreased motor activity but failed to alter the EEG pattern. The administration of either the low or high dose of apomorphine to SCH 23390-treated rats elicited a marked sedative response associated with EEG synchronization. The EEG synchronization produced by apomorphine (50 micrograms/kg) in SCH 23390-treated rats was prevented by (-)-sulpiride (25 mg/kg i.p.), a D-2 receptor blocker. It is concluded that by preventing the excitatory response to apomorphine SCH 23390 discloses the existence of a population of D-2 receptors mediating sedation and sleep.
Zetidoline (ZET), a rather selective dopamine (DA) D2-receptor blocker, was found to be equipotent to haloperidol and over 300 times as potent as sulpiride in activating the firing rate of substantia nigra dopaminergic neurons (SN-DA neurons) in unanesthetized rats. Moreover, like classic and atypical neuroleptics, ZET reversed and prevented apomorphine-induced inhibition of SN-DA neurons.
The administration of a small dose of apomorphine (50 micrograms/kg s.c.) induced repeated episodes of yawning in male rats. Short-term (3 days) treatment with 17 beta-estradiol antagonized apomorphine-induced yawning in male rats. Moreover, apomorphine induced yawning much less effectively in female than in male rats. These results suggest that both endogenous or exogenously administered estrogens induce subsensitivity of the DA receptors mediating yawning in rats.
A small dose of apomorphine (25 or 50 micrograms/kg, SC) induced repeated episodes of yawning, penile erection, genital grooming and a decrease in locomotor activity in rats. Hypophysectomy almost completely abolished yawning, penile erection and genital abolished yawning, penile erection and genital grooming but failed to modify the hypomotility induced by apomorphine. These results suggest that pituitary hormones are directly or indirectly involved in the apomorphine-induced yawning, penile erection and genital grooming but not in the sedative response to this drug.
Apomorphine (50 micrograms/kg) induced repeated episodes of yawning, penile erection and genital grooming in rats. A dose of cycloheximide, which inhibited brain protein synthesis by 50% totally prevented apomorphine-induced yawning and reduced by approximately 50% the occurrence of episodes of penile erection and genital grooming. However, this treatment failed to modify the stereotyped behaviour induced by 200 micrograms/kg of apomorphine. These results suggest that protein synthesis is required for the behavioural effects of small doses of apomorphine.
The effect of fipexide, administered at different intervals after the learning trial of a single step-through type passive avoidance situation was studied. The administration of fipexide immediately after the learning trial resulted in a long-lasting facilitation of passive avoidance behaviour. On the contrary, the administration of this compound 1 h prior to the retention test failed to influence passive avoidance behaviour. The results suggest that fipexide facilitates memory consolidation but does not influence retrieval processes.