Opioid induced non-photic phase shifts of hamster circadian activity rhythms

Byku, Mirnela; Gannon, Robert L.

doi:10.1016/s0006-8993(00)02304-0

Cited by 30 publications

(21 citation statements)

References 39 publications

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“…The role of enkephalins in the circadian system has received increasing attention as δ‐opioid receptors were identified in the hamster‐SCN (Byku et al ., 2000) and the δ‐ and µ‐opioid agonists BW373U86, SNC‐80, morphine and fentanyl were found to induce phase shifts in hamsters or mice when administered during the day. Whereas morphine‐induced shifts were related to its direct effects on behavioural activity, phase shifts in response to BW373U86, SNC‐80 and fentanyl were argued to occur independent of their direct behavioural effects (Marchant & Mistlberger, 1995; Byku & Gannon, 2000a, b; Meijer et al ., 2000). These findings open a new and promising avenue to study the interplay between the circadian clock and the mechanisms that regulate drug abuse‐related behaviours.…”

Section: Introductionmentioning

confidence: 99%

The opioid fentanyl affects light input, electrical activity and Per gene expression in the hamster suprachiasmatic nuclei

Vansteensel

Magnone

Oosterhout

et al. 2005

Eur J of Neuroscience

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The suprachiasmatic nuclei (SCN) contain a major circadian pacemaker, which is regulated by photic and nonphotic stimuli. Although enkephalins are present in the SCN, their role in phase regulation of the pacemaker is largely unknown. The opioid agonist fentanyl, a homologue of morphine, is an addictive drug that induces phase shifts of circadian rhythms in hamsters. We observed that these phase shifts are blocked by naloxone, which is a critical test for true opioid receptor involvement, and conclude that opioid receptors are the sole mediators of the actions of fentanyl on the circadian timing system. A strong interaction between opioids and light input was shown by the ability of fentanyl and light to completely block each other's phase shifts of behavioural activity rhythms. Neuronal ensemble recordings in vitro provide first evidence that SCN cells show direct responses to fentanyl and react with a suppression of firing rate. Moreover, we show that fentanyl induces a strong attenuation of light-induced Syrian hamster Period 1 (shPer1) gene expression during the night. During the subjective day, we found no evidence for a role of shPer1 in mediation of fentanyl-induced phase shifts. Based on the present results, however, we cannot exclude the involvement of shPer2. Our data indicate that opioids can strongly modify the photic responsiveness of the circadian pacemaker and may do so via direct effects on SCN electrical activity and regulation of Per genes. This suggests that the pathways regulating addictive behaviour and the circadian clock intersect.

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Section: Introductionmentioning

confidence: 99%

The opioid fentanyl affects light input, electrical activity and Per gene expression in the hamster suprachiasmatic nuclei

Vansteensel

Magnone

Oosterhout

et al. 2005

Eur J of Neuroscience

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“…As well, other stimuli relevant to the particular organism (including novelty and/or activity‐mediated arousal and several neurochemicals such as neuropeptide Y (NPY), benzodiazepines, serotonin and opioids) can reset the clock during the subjective day when the SCN is unresponsive to light (Hastings et al. , 1998; Byku & Gannon, 2000; Meijer et al. , 2000).…”

Section: Introductionmentioning

confidence: 99%

Blockade of the NPY Y5 receptor potentiates circadian responses to light: complementaryin vivoandin vitrostudies

Yannielli

Brewer

Harrington

2004

Eur J of Neuroscience

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Neuropeptide Y (NPY) is delivered to the suprachiasmatic nuclei (SCN) circadian pacemaker via an input from the thalamic intergeniculate leaflet. NPY can inhibit light-induced responses of the circadian system of Syrian hamsters. Here we studied whether an antagonist to NPY receptors can be used to potentiate photic phase shifts late in the subjective night. First we determined by in situ hybridization that both NPY Y1 and Y5 receptor mRNA are expressed in the SCN of Syrian hamsters. Second, similar to our previous findings at Zeitgeber time 14 (ZT 14, where ZT 12 was the time of lights off), we found that NPY applied at ZT 18.5 onto the SCN region of brain slices maintained in vitro could block NMDA-induced phase advances of the spontaneous firing rate rhythm, and this blocking effect was probably mediated by the Y5 receptor, since co-application of Y5 receptor antagonists completely reversed the effect of NPY, while application of a Y1 receptor antagonist had no effect under the same conditions. Third, we found that co-treatment with a Y5 receptor antagonist in vivo (s.c., 10 mg/kg) not only reversed the effect of NPY applied to the SCN in vivo through a cannula but also significantly potentiated the light-induced phase advance in the absence of NPY. This is the first report of a NPY receptor antagonist having such an effect, and indicates that NPY Y5 receptor antagonists could be clinically useful for potentiating circadian system responses to light.

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“…Endogenous enkephalins, as well as opioid receptors of the δ subtype, have been found in the hamster IGL and SCN (Morin et al, 1992;Byku et al, 2000). Several opioids have been shown to induce phase shifts in hamster circadian activity rhythms (Byku and Gannon, 2000a;Byku and Gannon, 2000b;Meijer et al, 2000;Tierno et al, 2002).…”

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confidence: 99%

Differential Responses of Circadian Activity Onset and Offset Following GABA-ergic and Opioid Receptor Activation

et al. 2003

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The circadian pacemaker in the mammalian suprachiasmatic nuclei is responsive to photic and nonphotic stimuli. In the present study, the authors have investigated the response of activity onset and offset to application of nonphotic stimuli: the benzodiazepine midazolam and the opioid receptor agonist fentanyl. In correspondence with previous studies, both stimuli induced phase advances of the activity onset when given in the mid- to late subjective day. In contrast, activity offset did not phase advance following these injections. Injections during the early subjective day induced small phase delays of the activity onset, while large phase delays occurred in activity offset. Phase shifts, induced at both circadian time zones, were paralleled by an increase in the length of daily activity (alpha). The increase in a remained present during several days after the injection. The different kinetics in phase shifting of the activity onset and offset indicate complexity in phase-shifting behavior of the circadian pacemaker in response to nonphotic stimuli. Moreover, the data show responsiveness of the circadian system to GABA-ergic and opioid receptor activation, not only during the mid- to late subjective day but also during the early subjective day. The data implicate that the early subjective day is an interesting phase for analysis of molecular and biochemical processes involved in nonphotic phase shifting.

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Opioid induced non-photic phase shifts of hamster circadian activity rhythms

Cited by 30 publications

References 39 publications

The opioid fentanyl affects light input, electrical activity and Per gene expression in the hamster suprachiasmatic nuclei

The opioid fentanyl affects light input, electrical activity and Per gene expression in the hamster suprachiasmatic nuclei

Blockade of the NPY Y5 receptor potentiates circadian responses to light: complementaryin vivoandin vitrostudies

Differential Responses of Circadian Activity Onset and Offset Following GABA-ergic and Opioid Receptor Activation

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