Locomotor Activity In Hamsters Research Articles

Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

The dorsomedial nucleus (DMN) of the hypothalamus has been implicated in seasonal control of reproduction. Syrian hamsters with DMN lesions, unlike control hamsters, do not undergo testicular regression after transfer from a long day length (14 h of light per day; LD) to a short day length (8 h of light per day; SD). SDs also markedly reduce hamster locomotor activity (LMA). To assess whether the DMN is a component of the neural circuitry that mediates seasonal variation in LMA, neurologically intact males (controls) and hamsters that had sustained lesions of the DMN (DMNx) were housed in an LD or SD photoperiod for 26 weeks. DMNx that prevented testicular regression counteracted decreases in LMA during 8 to10 weeks of SD treatment; steroid-independent effects of SDs did not override high levels of LMA in DMNx males. As in previous studies, testosterone (T) restoration increased LMA in LD but not SD castrated control males. In the present study, T also failed to increase LMA in SD-DMNx hamsters. The DMN is not necessary to maintain decreased responsiveness of locomotor activity systems to T in SDs, which presumably is mediated by other central nervous system androgen target tissues. Finally, DMNx did not interfere with the spontaneous increase in LMA exhibited by photorefractory hamsters after 26 weeks of SD treatment. We propose that DMN is an essential part of the substrate that mediates seasonal decreases in LMA as day length decreases but is not required to sustain decreased SD responsiveness to T or for development of refractoriness to SDs.

The effects of leptin hormone on locomotor activity in Syrian hamsters (Mesocricetus auratus)

The suprachiasmatic nucleus (SCN) generates and controls the circadian rhythms in mammals including the rhythm of locomotor activity. Leptin is a hormone secreted by adipose tissue that informs the brain about the fat stores. SCN neurons express leptin receptors. Here we investigated the effects of 3 different leptin administrations on the locomotor activity of the Syrian hamsters maintained in constant darkness. Animals were intraperitoneally (ip) injected (4 µg/kg), subcutaneously (sc) infused (4 µg/kg), or intra-SCN infused (0.4 µg/kg) with leptin for 3 days at circadian time 10 whereas the controls received saline (0.9% NaCl) at the same time in order to eliminate stress factors. Our results demonstrate that the locomotor activity of the hamsters can be phase advanced by the external leptin administrations. Leptin affected the level of phase-shifts in an administration method-dependent manner. The biggest phase advance was observed in intra-SCN infusion (P = 0.001), and the smallest was in the ip injection (P = 0.041) group. The wheel-turn amounts did not change significantly in the groups before and after the leptin administrations (P = 0.233); however, the period lengths increased (P = 0.011) significantly after leptin administrations. These results suggest for the first time that in vivo leptin administrations may change the rhythm of locomotor activity in adult male Syrian hamsters.

Entrainment and coupling of the hamster suprachiasmatic clock by daily dark pulses

The circadian rhythm of locomotor activity of hamsters kept in constant light (LL) can split into two distinct components that, in steady state, lie 180 degrees apart. The splitting phenomenon is the result of antiphase circadian oscillations between left and right sides of the suprachiasmatic nuclei (SCN), the master circadian clock in mammals. In unsplit hamsters housed in LL, a single dark pulse produces a phase-shift of the wheel-running activity rhythm, accompanied by a transient down-regulation of clock gene expression in the SCN. In the present study, we evaluated the effects of daily 1-hr dark pulses on wheel-running activity rhythm and on the expression of clock and nonclock proteins in the SCN of Syrian hamsters exposed to LL conditions. The results show that a daily 1-hr dark pulse entrained the rhythm of wheel-running activity of unsplit hamsters. In addition, in split animals, unimodal coupling of the two locomotor activity components was produced by daily 1-hr dark pulses. In the SCN, the effects of entrainment and unimodal coupling of the two separate components by dark observed in behavior were also evident in the bilateral expression of the proteins c-FOS, p-ERK, PERIOD 1, and calbindin. These results show that the bilaterally asymmetric SCN clock, underlying split circadian behavior, can be recoupled in phase and entrained by short daily dark exposure, indicating the synchronizing potency of darkness on the main circadian clock.

The selective neurokinin 1 receptor antagonist R116301 modulates photic responses of the hamster circadian system

The recent development of selective NK 1 receptor antagonists that are active in vivo provides an important research tool to examine the role of substance P in the regulation of circadian rhythmicity. First, we tested whether R116301 {(2R- trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]- N-(2,6-dimethylphenyl)-1-acetamide (S) hydroxybutanedioate}, a new selective NK 1 antagonist, alters the phase-shifting effects of light. Hamsters housed in constant darkness were injected with different doses of R116301, just before being exposed to a light pulse during the subjective night. The results were compared with those obtained with the NK 1 antagonist L-760,735 {2-(R)-(1-(R)-3,5-bis(trifluoromethyl)phenyl)ethoxy)-4-(5-(dimethylaminomethyl)-1,2,3-trioazol-4-yl)methyl-3-(5)-phenyl)morpholine}. Second, the effects of the NK 1 antagonists R116301 or L-760,735 injected immediately after exposure to a light pulse were similarly determined. Third, we investigated whether R116301 or L-760,735 injected during the mid-subjective day or the late subjective night can phase-shift the circadian rhythm of locomotor activity in hamsters housed in constant light. Both compounds reduced, by more than 30%, the phase-advancing effects of a light pulse in hamsters otherwise maintained in constant darkness, only when the drugs were administered before the light pulse. Under constant light conditions, both NK 1 receptor antagonists induced significant phase-advances when injected during the subjective day, but not during the subjective night. The present results indicate that tachykinergic neurotransmission modulates the photic responses of the circadian system upstream of phase resetting mechanisms and suggest that an inhibition of the NK 1 receptor signals “darkness” to the circadian clock.

The Effect of Amphetamine on Locomotion Depends on the Motor Device Utilized: The Open Field vs. the Running Wheel

DELLA MAGGIORE, V. AND M. R. RALPH. The effect of amphetamine on locomotion depends on the motor device utilized: The open field vs. the running wheel. PHARMACOL BIOCHEM BEHAV 65(4) 585–590, 2000.—The effect of amphetamine on the level of locomotion exhibited on two different motor devices was examined in the Golden hamster. Increasing concentrations of the psychostimulant from 4 to 10 mg/kg significantly enhanced locomotor activity in hamsters exposed to an open field. A further increase to 25 mg/kg inhibited ambulatory activity to levels below the control baseline, while augmenting the occurrence of stereotypic behaviors. The activating effect of amphetamine on ambulatory activity was observed regardless of the time of testing (day or night) or lighting condition, with no apparent modulation by the circadian system. On the other hand, home-cage wheel-running activity was maximally inhibited by 10 mg/kg amphetamine, whereas a smaller dosage (1.5 mg/kg) had no effect over the wheel-running activity baseline of saline controls. Although both the running wheel and the open field quantify locomotion, the dissociation obtained shows that they measure different components of it. The results are interpreted within Lyon and Randrup's hypothesis on the actions of amphetamine (16).

No evidence for extraocular photoreceptors in the circadian system of the Syrian hamster.

Campbell and Murphy reported recently that 3 h of bright light (13,000 lux) exposure to the area behind the knee caused phase shifts of the circadian rhythms of both body temperature and saliva melatonin in humans. The authors tested the hypothesis that extraocular photoreception is also involved in the circadian system of the Syrian hamster. Hamsters were bilaterally enucleated (eyes removed), and their backs were shaved. Hamsters with stable free-running rhythms in constant darkness were exposed to direct sunlight for 1 or 3 hours during their subjective night. Intact (control) animals showed phase shifts as expected, but the locomotor activity of enucleated animals was unaffected by the exposure to sunlight. The authors also measured the pineal melatonin content after exposure to sunlight. Pineal melatonin content in intact animals declined markedly as expected, but no decline was observed in the enucleated hamsters. The authors conclude that extraocular phototransduction is not capable of shifting the phase of the hamster's locomotor activity rhythm or of suppressing pineal melatonin synthesis.

Masking of locomotor activity in hamsters.

The inhibition of locomotion by light (masking) was investigated in Syrian hamsters. When 1-h pulses of light were presented in the early night, activity was strongly suppressed by irradiances of about 1 lx or greater. Ultradian light-dark cycles were used as another way to study masking. Hamsters were unable to entrain to 3.5:3.5-h light-dark cycles, thus permitting the masking and the entraining effects of light to be distinguished. Light had greater suppressive effects on activity in home cages than on activity in novel running wheels. Moreover, in home cages activity remained very low for about 30 min after lights were turned off. Post-pulse suppression of activity was not simply a consequence of reduced running, as shown by experiments in which running was temporarily prevented by locking the wheels. A phase response curve for masking was obtained by placing hamsters in novel wheels for 3-h periods at various times throughout their circadian cycles, and then superimposing a 30-min light pulse. The suppressive effect of light was maximal around the onset of activity, which normally coincides with dusk in hamsters. This may have adaptive value in limiting foraging to the hours of darkness.

Phase-shifting effect of 8-OH-DPAT, a 5-HT1A/5-HT7 receptor agonist, on locomotor activity in golden hamster in constant darkness

The present results show that under constant darkness the endogenous circadian pacemaker located in the suprachiasmatic nuclei can be affected by administration of 8-hydroxy-2-[di-n-propylamino] tetralin (8-OH-DPAT), a well known 5-HT1A/5-HT7 receptor agonist. A single i.p. injection (0.1 ml) with 8-OH-DPAT (5 mg/kg) induced significant phase-advances of hamster locomotor activity at circadian time (CT) 6 and 8 and a significant phase-delay at CT11. Saline injections by themselves induced a significant phase-advance at CT10-11. The dose-response curve for 8-OH-DPAT showed a maximal phase-shifting effect for doses of at least 2.5 mg/kg at CT8. Thus, in golden hamsters, (1) 8-OH-DPAT has a chronobiological effect with sensitivity depending upon the circadian time of injection, and (2) a single saline injection is able to induce regular phase-advances at the end of the subjective day (CT10-11).

Neuropeptides phase shift the mammalian circadian pacemaker

We studied the influence on circadian rhythms of peptides that have been reported to be colocalized in suprachiasmatic nucleus (SCN) neurons. Gastrin-releasing peptide (GRP1–27), peptide histidine isoleucine (PHI), and vasoactive intestinal polypeptide (VIP) were microinjected into the suprachiasmatic nucleus (SCN) region of Syrian hamsters free running under three different constant lighting conditions. All peptide injections caused phase-dependent phase shifts of hamster locomotor activity rhythms which were unaffected by constant lighting conditions. GRP1–27 (150 pmol) caused large phase delays when injected at circadian times (CT) 12–16, modest phase advances when administered at CT20–24, and few shifts during the subjective day. Injections of saline vehicle at any of these phases caused only very small phase shifts. Phase delays induced by GRP1–27 at CT12–14 were dose dependent, unrelated to injection volume (at a constant dose), and attenuated by pretreatment with the BN/GRP-preferring receptor antagonist BIM 26226. VIP (150 pmol) caused moderate phase delays at CT12–14 and moderate phase advances at CT20–24. PHI (150 pmol) caused moderate phase delays at CT12–14 only. Coadministration of 150 pmol of GRP1–27, PHI, and VIP in an equimolar neuropeptide cocktail (50 pmol of each peptide) caused phase delays at CT12–14 and phase advances at CT20- 24 which did not differ from those induced by 150 pmol of GRP1–27 alone at these phases. The shifts induced by 150 pmol of the peptide cocktail were smaller than the sum of the shifts induced by 50 pmol doses of each peptide administered separately at those phases. Since the phase- delaying effects of the cocktail were weaker than the summed effects of the component 50 pmol doses of the peptides, these data demonstrate a lack of synergism among the effects of these peptides. Since GRP1–27 (150 pmol) evoked shifts similar in magnitude to those of the cocktail, there is no evidence that these apparently colocalized neuropeptides must interact to exert maximal effects on the circadian pacemaker.

A serotonin neurotoxin attenuates the phase-shifting effects of triazolam on the circadian clock in hamsters

Several lines of evidence suggest the potential involvement of serotonergic pathways in mediating the effects of activity-inducing stimuli on the circadian clock in rodents. The aim of the present 3 experiments was to examine the effects of the serotonergic neurotoxin, p-hloroamphetamine (PCA, 10 mg/kg) on: (1) the monoamine levels of the hypothalamus, frontal cortex and hippocampus in the hamster; (2) the phase shifts in the circadian rhythm of locomotor activity of hamsters in response to treatment with the short-acting benzodiazepine, triazolam (7.5 mg/kg); and (3) the magnitude of the acute increase in locomotor activity associated with triazolam administration in this species. The administration of PCA to hamsters caused changes of specific monoaminergic systems in the hypothalamus, that were limited to a selective decrease in serotonin levels 7 days post-treatment. The phase shifts of the circadian clock in response to triazolam treatment at CT 6 were considerably attenuated following the administration of the 5-HT neurotoxin. The total amount and the profiles of triazolam-induced wheel-running and general cage activity between CT 6 and CT 12 were not significantly affected by the PCA treatment. The finding that a 5-HT neurotoxin can attenuate the phase-shifting effects of triazolam in hamsters, without interfering with its activity-inducing properties, suggests that serotonergic afferents might be involved in the mechanism for non-photic phase-shifting of the circadian system.

Effects of the 5-HT 1a receptor agonist 8-OH-DPAT and other non-photic stimuli on the circadian rhythm of wheel-running activity in hamsters under different constant conditions

Our findings show that administration of the 5-HT 1A receptor agonist 8-OH-DPAT (8-hydroxy-2[di- n-propylamino] tetralin) was able to induce significant phase-advances 4 h before onset of hamster locomotor activity under constant darkness. All other non-photic treatments applied such as melatonin, dimethyl sulphoxide, Ringer, saline or enforced wheel-running failed to induce any significant phase-advances. Similar results were obtained in pinealectomized animals. In constant light (LL), all treatments produced phase-advances. These results show that: (1) LL seems to be an inappropriate constant condition to study the chronobiological effect of drugs or other non-photic stimuli; (2) the endogenous circadian pacemaker (SCN) can be affected specifically by 8-OH-DPAT.

Wheel running raises body temperature and changes the daily cycle in golden hamsters

The purpose of this study was to characterize the influence of wheel-running activity on temperature circadian rhythm in golden hamsters. Amplitude of body temperature rhythm was significantly higher in animals that had access to the running wheel. Qualitatively, wheel running resulted in squaring of temperature rhythm waveform, a phenomenon that was independent of ambient illumination. When the hamsters had access to an immobilized wheel, the effect on temperature was no longer observed. Fast Fourier Transformation after subtracting 24-h sine waveforms (to rule out harmonics of the principal frequency), indicated distinct secondary components of the rhythms, i.e., a 12-h component in animals that had access to the wheels and an 8-h component in animals that did not. The rise in body temperature could be dissociated from the start of the activity period, body temperature augmenting before the time of light-dark transition, while activity increased about 12 min later. On the first night after presentation of an estrous female, the temperature cycle in male hamsters that did not access to the wheels was similar to that found in animals running on the wheels; the effect was no longer observed in subsequent nights. The results contribute to the view that the spontaneous locomotor activity in hamsters has a significant effect on temperature cycle.

Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism.

We endeavored to determine whether three behavioral effects of melatonin in rodents, i.e., depression of locomotor activity in hamsters, analgesia in mice, and impairment of 3-mercaptopropionic acid (3-MP) convulsions, exhibited the time dependency known to occur for several neuroendocrine effects of the hormone. Activity was monitored and registered by means of an optical actometer, and analgesia was assessed by the hot-plate procedure. Locomotor activity, analgesia, and seizure susceptibility were maximal at the beginning of the scotophase and minimal at noon. The effects of melatonin on the three parameters peaked at early night. The administration of the benzodiazepine antagonist flumazenil, although unable by itself to modify locomotor activity, pain, or seizure threshold, blunted the activity of melatonin. These results suggest that the time-dependent effects of melatonin on specific rodent behaviors may be mediated by central synapses employing gamma-aminobutyric acid (GABA) as an inhibitory transmitter.

Effects of cholecystokinin on morphine-elicited hyperactivity in hamsters

The effects of the octapeptide cholecystokinin (CCK) on hamster locomotor activity were investigated in three experiments. In Experiment 1, the effect of CCK (25, 50, 75 μg/kg) on morphine (2.5 mg/kg)-elicited hyperactivity was studied. Results indicated that CCK antagonized morphine-elicited hyperactivity and that CCK alone elicited hypoactivity. There were no effects of dose of CCK. In Experiment 2, the effects of intraperitoneal (IP) and subcutaneous (SC) routes of administration of CCK (25 μg/kg) on locomotor activity were studied. Compared to saline controls, CCK induced hypoactivity that was of greater magnitude and of longer duration when administered IP than SC. Experiment 3 was designed to replicate the route of administration effect observed in Experiment 2 and to determine whether sensitization to CCK-induced hypoactivity develops over the course of a few injections. Results indicated that CCK-induced hypoactivity was greater after IP than SC administration but that sensitization was not detectable. It is concluded that CCK antagonizes morphine-elicited hyperactivity in the hamster by acting, in part, independently of morphine to produce opposite behavioral effects.

Melatonin-induced depression of locomotor activity in hamsters: Time-dependency and inhibition by the central-type benzodiazepine antagonist Ro 15-1788

The aim of the present study was to determine whether melatonin-induced depression of locomotor activity in hamsters is time-dependent and to analyze the inhibitory effects of the central-type benzodiazepine (BZP) antagonist Ro 15-1788 on melatonin-induced depression of locomotor behavior. Activity was monitored and registered by means of an optical actometer. Two phases of locomotor behavior were found. The initial phase, found both at noon and during the evening, exhibited an absence of diurnal variability, while a second long-lasting phase of activity exhibited a peak at early night. The IP injection of melatonin (minimal effective dose: 100 μ/kg) inhibited the early phase of activity at 1200 or 2000 h. Inhibition of the late phase of activity was found at 2000 or 0400 h, but not at midnight. When assessed at 2000 h, melatonin depression of the early phase of locomotor activity attained significance after 5 days of injection, while its effect on the late phase of activity attained significance during the second day of injection. The administration of Ro 15-1788, although unable by itself to modify locomotor activity, significantly attenuated the inhibitory effects of melatonin. These results indicate the existence of a time-dependency for melatonin activity on locomotor behavior similar to that known to occur for other effects of the hormone, and further support a link between melatonin and the activity of central type BZP receptors.

The effects of short periods of immobilization on the hamster circadian clock

Recent findings indicate that stimuli which induce an acute increase in locomotor activity can induce phase shifts in the circadian clock of hamsters. Support for the actual role of the acute increase in activity in the mediation of these phase shifts is provided by the observation that immobilization can totally block phase shifts in the activity rhythm that are normally induced in response to exposure to two of these stimuli, either a pulse of darkness or an injection of a benzodiazepine. In order to further examine the effects of immobilization on the circadian system of hamsters, 3 studies were carried out. In a first study, the effects of a 3-h period of immobilization procedure on the phase of the free running circadian rhythm of locomotor activity were tested at 8 different circadian times. Immobilization during the highly active part of the animal's activity cycle resulted in phase delays in the activity rhythm, while immobilization at other circadian times had little or no effect on the circadian time-keeping system. In two other studies, we reported that immobilization had no effect on phase shifts normally induced by 3-h pulses of light or injections of the protein synthesis inhibitor, cycloheximide, two stimuli that are clearly not associated with an increase in locomotor activity in hamsters. Thus, the ability of immobilization to block stimulus-induced phase shifts in the circadian clock appears to be specific to those stimuli that induce an acute increase in locomotor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Influences of the paraventricular and suprachiasmatic nuclei and olfactory bulbs on melatonin responses in the golden hamster.

Removal of the pineal, or denervation of this gland by superior cervical ganglionectomy, blocks testicular regression in golden hamsters exposed to short photoperiods. Aspiration of the olfactory bulbs or lesions of the suprachiasmatic or paraventricular nuclei of the hypothalamus (SCNx or PVNx) have similar effects. We have examined the effects of these operations on pineal melatonin content and gonadal responses to various patterns of exogenous melatonin in order to examine the roles played by the olfactory bulbs, the SCN, and the PVN in hamster photoperiodism. SCNx and PVNx significantly reduced pineal melatonin content throughout the dark phase, while bulbectomy did not significantly affect melatonin concentrations at the time of the nocturnal peak. Bulbectomy significantly delayed the nightly onset of locomotor activity in hamsters exposed to 14L:10D, but not that of animals housed in 10L:14D. Although bulbectomy reduced the gonadal response to one or three daily injections of melatonin, these individuals exhibited significant testicular regression in response to melatonin as long as injections fell in the evening. In contrast, destruction of the PVN rendered hamsters unresponsive to one daily melatonin injection, but equally responsive to three injections, regardless of the time of day at which these injections were given. Whereas exposure of bulbectomized hamsters to 30 weeks of short days made them refractory to subsequent melatonin challenge, PVNx hamsters remained sensitive to appropriately timed melatonin treatments regardless of their photoperiodic history. Many, but not all hamsters that experienced complete SCN lesions remained sensitive to three daily melatonin injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitor of protein synthesis phase shifts a circadian pacemaker in mammalian SCN.

The suprachiasmatic nucleus (SCN) of the hypothalamus contains a circadian pacemaker that regulates many circadian rhythms in mammals. Experimental work in microorganisms and invertebrates suggests that protein synthesis is required for the function of the circadian oscillator, and recent experiments in golden hamsters suggest an acute inhibition of protein synthesis can induce phase shifts in a mammalian circadian pacemaker. To determine whether protein synthesis in the SCN region is involved in the generation of circadian rhythms in mammals, a protein synthesis inhibitor, anisomycin, was microinjected into the SCN region, and the effect on the circadian rhythm of locomotor activity of hamsters was measured. A single injection of anisomycin into the SCN region induced phase shifts in the circadian activity rhythm that varied systematically as a function of the phase of injection within the circadian cycle. These results suggest that protein synthesis may be involved in the generation of circadian rhythms in mammals and that the anatomic site of action of anisomycin is within the hypothalamic suprachiasmatic region.

Effects of stress on morphine-elicited locomotor activity in hamsters.

Two experiments were conducted to investigate the effects of stress on morphine-elicited locomotor activity in hamsters. In Experiment 1, half of the animals were habituated to handling and injection procedures (low-stress condition) and half were not (high-stress condition) prior to 6 days of testing with a low dose (2.5 mg/kg) of morphine. On the first test day, morphine elicited hyperactivity among habituated animals, whereas among nonhabituated animals morphine elicited hypoactivity. The effects of handling diminished across test days, so that on the last test day, morphine elicited hyperactivity in both habituated and nonhabituated animals. In Experiment 2, the effect of a noise stressor on activity elicited by three doses of morphine (2.5, 5.0, and 15 mg/kg) was investigated. Half of the animals were tested under conditions of low noise stress (70 dB), and half were tested under conditions of high noise stress (90 dB). Results indicated that the effects of each dose of morphine were potentiated in the high-stress relative to the low-stress condition. Both experiments demonstrated that environmental stressors can potentiate the response to exogenous opiate administration in hamsters. Moreover, the results are consistent with the hypothesis that stress induces the release of endogenous opioids which summate with exogenous opiates to determine the final effective dose.

Effects of stress on morphine-elicited locomotor activity in hamsters.

Effects of stress on morphine-elicited locomotor activity in hamsters.