haut de page

mise à jour du
5 février 2004
 Physiology & Behavior
Modulation by sudden darkness of
apomorphine-induced behavioral responses
AG Nasello, AS Sassatani, FS Ferreira, LF Felicio, CA Tieppo
Departamento de Ciências Fisiologicas da Faculdade de Ciências Médicas da Santa Casa de Sào Paulo Brazil

Gamberini MT, Bolognesi ML, Nasello AG. The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming. Neuroscience Letters 2012; 531:91-95
-Gamberini MT, Gamberini MC, Nasello AG. Involvement of dopaminergic and cholinergic pathways in the induction of yawning and genital grooming by the aqueous extract of Saccharum officinarum L. (sugarcane) in rats. Neuroscience Letters 2015;584:270-275
-Naselo A, Tieppo C, Felicio L Apomorphine induced yawning in the rat : influence of fasting and time of day Physiology & Behavior 1995;57(5):967-971
-Nasello AG et al Modulation by sudden darkness of apomorphine-induced behavioral responses Physiology & Behavior 2003;78:521-525
Introduction : Light intensity influences almost all physiological and behavioral processes. These influences are responsible for some biological rhythms, especially those related to the light-dark cycle, with circadian rhythm being one of the better known. It is classically recognized that the release of neurotransmitters and the secretion of hormones vary according to circadian rhythms. These variations are among the major causes of physiological and behavioral modifications induced by light intensity variations. The oestrous cycle of some laboratory and farm animal species can be synchronized by manipulation of photoperiodism. In rodents, core body temperature and motor activity are known to be well synchronized with each other under 12-h light- 12-h dark and 12-h light-light and 12-h darkdark conditions. During lactation and during critical postnatal periods, variations of light conditions modify the circadian organisation of motor activity of adult animal. There is a relationship between circadian changes in spontaneous motor activity and dorsal vs. ventral striatal dopamine neurotransmission. Circadian fluctuations in dopamine levels and receptor density, as well as in alpha and beta-adrenergic receptor density in rat brain, have also been described. Photoperiodism also modifies drug effects and their pharmacokinetics.
To study the effects of light intensity on variables such as sex, stress conditions, age, and strains may be of crucial importance. In humans, although they have increasingly insulated themselves from natural cycles of light or darkness, some psychiatric syndromes are related to or influenced by photoperiod and light intensity. Seasonal affective disorder, a mood disorder involving a recurring autumn and/or winter depression may be treated by phototherapy but this treatment is not beneficial to normal individuals. In non-seasonal depression, mood typically fluctuates daily, with improvement over the course of the day, influenced by light intensity. Sudden darkness in rats is equivalent to sudden lightness in humans. Phototherapy, that is, submission of patients to sudden increase of light intensity is one of the treatments for depression and in particular, for seasonal affective disorders. On the other hand, this kind of treatment is not favorable for normal individuals. Bright light interventions tended to make normal elderly women feel worse-more irritable, anxious, and agitated. In other words, sudden light changes may be useful in the treatment of some psychiatric and neurological disorders or may impair others depending on the mechanisms involved.
Although there is a large database relating light intensity and behaviour, studies on sudden darkness are less frequent. In the past, this model has been used to evaluate peptide action on dopaminergic systems. In a previous paper, it bas been described that sudden darkness increases general motor activity and it diminishes habituation, fear, and anxiety. In addition, as it has been described, sudden darkness can be used as an experimental tool to modify behavioral parameters without using drugs. The aim of the present study was to investigate the role of dopaminergic mechanisms involved in the effects of sudden darkness using a pharmacological approach. For this purpose, we evaluated the effects of sudden darkness on behaviors elicited by a large scope of apomorphine (APO) doses, 0.05 mg/kg being the lowest and 0.6 mg/kg being the highest, such as yawning-penile erection syndrome (YES), general activity, and stereotypy.
Discussion : Sudden darkness is able to induce an outstanding increase of general activity. The mechanisms underlying this phenomenon are unknown. The behavioral changes are so fast that only changes in neurotransmission may be responsible for them. We focused on dopaminergic systems because there is a direct relation between general activity and dopaminergic activity and responses to light intensity changes are often related to dopamine.
The behavioral responses to dopaminergic receptor stimulation are well known. Low doses of dopamine elicited yawning, suppression of exploration, and penile erection (YES). These are behavioral patterns that occur concomitantly under some conditions. After that, by progressively increasing dopamine concentrations, a typical bell-staped dose-response curve of general motor activity is observed, i.e., hypo-hyper-hypo-mobility.
In other words, the YES is reduced, exploration starts and continues to increase until it totally replaces the YES, and then maximal general activity is observed. Later on, mobility starts to decrease and is replaced with stereotyped behaviors until maximal stereotypy is reached. The same prototype of behavioral responses is obtained using APO, a full and nonspecific dopaminergic agonist.
In the present paper, we showed that sudden darkness was able to, modify some spontaneous behaviors and also modulated several APO-induced behavioral effects. We used APO in a dose range between 0.05 and 0.60 mg/kg.
The influence of sudden darkness on the effects of pre(0.05 and 0.1 mg/kg) and post-synaptic doses (0.25, 0.45 and 0.6 mg/kg) of APO was tested. Pre-synaptic doses were assayed in YES (0.05 and 0. 1 mgikg) and motor activity (0.05 mg/kg). Post-synaptic doses were evaluated in motor activity (0.25 mg/kg) and stereotyped behaviour (0.45 and 0.6 mg/kg). Spontaneous total and genital grooming of male and female rats was also recorded.
The YES is a physiological response that can be used as an experimental tool to elucidate mechanisms of actions of drugs and hormones. Although the syndrome is related to various neurotransmitters, dopamine is particularly involved. There is controversy about the subtype of dopamine receptor involved. The D2 subtype appears to be the main receptor involved, but the participation of the D1 receptor alone or simultaneously activated with the D2 receptor cannot be dismissed. Moreover, expression of YES may be due to the stimulation of D2 autoreceptors of nigrostriatal dopaminergic neurons, although we should also consider the D2 post-synaptic stimulation of the paraventricular nucleus of the hypothalamus. In any case, this syndrome only becomes visible with the lowest stimulation of dopaminergic systems. Sudden darkness diminished total yawns obtained with 0.05 and 0. 1 mg/kg of APO in a dose-related manner. These facts suggest an activation of the dopamine responses involved that could shift these responses to mobility. No other parameter of YES was modified.
Taken together, these results may indicate that, albeit triggered by the same stimuli, different pathways are involved in yawning and penile erection, as proposed by Gamberini et al. The effect of sudden darkness on APO-induced yawning was the opposite of that observed when this parameter was recorded during the dark time of the day. This suggests that the effects of abrupt changes in light intensity differ from those of light conditions corresponding to the circadian rhythm. One of the factors included in the YES is genital grooming. In this situation, genital grooming is a consequence of penile erection and cannot be correlated with spontaneous grooming. Like all the other variables linked to penile erection, it was not modified, by sudden darkness. In almost all species of animals, spontaneous grooming has important physiological functions and a significant meaning in social interaction and social organization. It is also a factor related to sex. Dopamine is implicated in the expression of this behavior with different participations of its receptor subtypes. Sudden darkness increased spontaneous total and genital grooming of male rats but had no effect on either kind of grooming of female rats. This sexual dissimilarity can be explained by the tact that sudden darkness increased motor activity in female rats more than in male rats. That is, part of the time spent in locomotion by female rats is substituted by grooming in male rats.
Spontaneous motor activity is the result of the interactions of a myriad of peripheral and central variables. Among them, dopamine is certainly one of the most important. Sudden darkness augmented locomotion and rearing, diminished immobility but did not modify total groommg, as previously reported. Hypo-mobility induced by 0.05 mg/kg was not altered by sudden darkness. However, the increase in locomotion and rearing and the decrease in immobility time observed under sudden darkness, even though nonsignificant, may be correlated with the decrease in yawning observed with the same APO dose.
Animals treated with 0.25 mg/kg were clearly divided into two groups, i.e., hypo- and hyper-responsive. Under light conditions, both groups were different from the control but did not differ from one another. Sudden darkness enhanced the locomotion of the hypo-responsive group compared to control. Sudden darkness reduced the locomotion of hyper-responsive animals, a tact that may be explained by overstimulation of dopaminergic systems that shifts general activity to stereotyped behaviors. Locomotion responses to sudden darkness by hypo- and hyper-responsive rats suggest that sudden darkness potentiated the responses to APO. Rearing and grooming were reduced in both groups; in hypo-reactive rats, this may perhaps have been due to the increase of locomotion and in hyper-reactive animals, iît may have been due te, the surge of stereotyped behaviors. No differences were observed in immobility duration.
Stereotypy is the major behavioral response induced by dopaminergic stimulation. The circadian lightdark cycle modified stereotypy with highest responses at 1300 and 1700 h. Stereotyped behaviors induced by 0.45 and 0.60 mg/kg of APO were similar and were not modified by sudden darkness. Probably, physiological changes elicited by sudden darkness are unable to modify this strong pharmacological response.
In a previous paper, we proposed sudden darkness as an experimental tool to modify motor activity and anxiety. Now, we show that other behaviors can be modulated by sudden darkness. Animal models based on spontaneous behavior or ethologically based models may be more sensitive to behavioral responses.
Our results may be due to a sudden darkness-induced physiological release of dopamine. This hypothesis is based on data showing that sudden darkness diminishes pre-synaptic responses to APO and increases lower post-synaptic responses such as motor activity without modifying higher post-synaptic responses such as stereotyped behavior. Experiments to confirm this hypothesis by microdialysis procedures are being done in our laboratories. Physiological release of dopamine may be useful in the treatment of psychiatric and neurological disorders or may impair others depending on dopaminergic mechanisms involved in the pathophysiology of the diseases. It must be taken into account that sudden darkness in rats is equivalent to sudden lightness in humans.
-Naselo A, Tieppo C, Felicio L Apomorphine induced yawning in the rat : influence of fasting and time of day Physiology & Behavior 1995; 57; 5; 967-971
-Seki Y, Y Nakatani, et al Light induces cortical activation and yawning in rat Behav Brain Res 2003; 140; 1-2; 65-73
-Gamberini MT, Bolognesi ML, Nasello AG. The modulatory role of M2 muscarinic receptor on apomorphine-induced yawning and genital grooming. Neurosci Lett. 2012