Induction of a Citrus gene highly homologous to plant and yeast thi genes involved in thiamine biosynthesis during natural and ethylene-induced fruit maturation

In response to a light pulse, hamsters normally generate phase advances that are positively correlated with the length of their circadian period (tau). To determine whether this is a general property of the phase-shifting oscillator, the present study looked for a correlation between tau and phase-advance size not only for photic but also for nonphotic shifts. Syrian hamsters, Mesocricetus auratus, were entrained to light-dark cycles with a periodicity of either 23.67 h (the short-T group) or 24.33 h (the long-T group); after release into constant darkness, the short-T and long-T groups exhibited short and long taus, respectively. These animals were then induced to run in a novel exercise wheel for 3 h, starting at circadian time (CT) 7, or were exposed to 20 min of light, starting at CT 19. The size of the ensuing phase advances did not differ between the short-T and long-T groups not only for the nonphotic stimulus but also for the photic one, an unexpected result for the photic stimulus. Within the short-T groups for photic and nonphotic stimuli, the shorter tau was, the larger the phase advances were, another unexpected relationship. Another experiment where phase delays were induced by light pulses at CT 15 also failed to yield significant differences between the short-T and long-T groups. Independently of their after-effects on tau, T cycles may influence the capacity of the pacemaker to phase shift in ways that are still unclear but at least similar for both photic and nonphotic shifts.     

Conditioned stimulus control in the rat circadian system depends on clock resetting during conditioning.

The authors examined the ability of a conditioned stimulus (CS; mild air disturbance) previously paired with an entraining light pulse to reset the circadian pacemaker in rats. Rats were entrained to a single 30-min light stimulus delivered every 25 hr or 24 hr (T cycle). Each daily light presentation was paired with the CS. After at least 20 days of stable entrainment to each of the T cycles, the rats were allowed to free run and were then presented with the CS at circadian time 15. CS-induced phase shifts in wheel-running activity rhythms were taken as evidence for conditioning. For the most part, conditioning occurred after CS-light pairings on the 25-hr but not 24-hr T cycle. The results suggest that CS control of the circadian clock phase depends on the effect that the entraining light pulse has on the clock during conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Roles of suprachiasmatic nuclei and intergeniculate leaflets in mediating the phase-shifting effects of a serotonergic agonist and their photic modulation during subjective day

Serotonin (5-HT) has been implicated in the phase adjustment of the circadian system during the subjective day in response to nonphotic stimuli. Two components of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian clock) and the intergeniculate leaflet (IGL), receive serotonergic projections from the median raphe nucleus and the dorsal raphe nucleus, respectively. Experiment 1, performed in golden hamsters housed in constant darkness, compared the effects of bilateral microinjections of the 5-HT1A/7 receptor agonist, 8-hydroxydipropylaminotetralin (8-OH-DPAT; 0.5 microgram in 0.2 microliter saline per side), into the IGL or the SCN during the mid-subjective day. Bilateral 8-OH-DPAT injections into either the SCN or the IGL led to significant phase advances of the circadian rhythm of wheel-running activity (p < .001). The phase advances following 8-OH-DPAT injections in the IGL were dose department (p < .001). Because a light pulse administered during the middle of the subjective day can attenuate the phase-resetting effect of a systemic injection of 8-OH-DPAT, Experiment 2 was designed to determine whether light could modulate 5-HT agonist activity at the level of the SCN and/or the IGL. Serotonergic receptor activation within the SCN, followed by a pulse of light (300 lux of white light lasting 30 min), still induced phase advances. In contrast, the effect of serotonergic stimulation within the IGL was blocked by a light pulse. These results indicate that the respective 5-HT projections to the SCN and IGL subserve different functions in the circadian responses to photic and nonphotic stimuli.     

Brain noradrenergic responses to footshock after chronic activity-wheel running.

Effects of physical activity on brain noradrenergic response to footshock were examined. Male Fischer 344 rats were randomly assigned to shoebox cages with (AW) or without (SED) 24-hr access to an activity wheel for 4–5 weeks. Extracellular levels of norepinephrine (NE) and 3,4-dihydroxyphenyl-acetic acid (DOPAC) in the brain frontal cortex were measured in 20-min samples of microdialysate taken during a 2-hr baseline, 40 min of scrambled footshock, and a 1-hr recovery. Levels of messenger RNA (mRNA) for tyrosine hydroxylase (TH), c-fos, and prepro-galanin in the locus coeruleus were measured by in situ hybridization histochemistry with autoradiographic analysis. NE levels were the same for SED and AW rats at baseline but were elevated in SED compared with AW during and after footshock. Levels of mRNA for TH and c-fos were elevated after footshock but did not differ between SED and AW. Our findings suggest that wheel running blunts NE release in the brain frontal cortex in response to footshock but does not influence expression of the gene that encodes TH in the locus coeruleus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Managed care and medication compliance: implications for chronic depression

Syrian hamsters, Mesocricetus auratus, were confined to novel running wheels for a 3-h period, starting at approximately circadian time (CT) 4.5 (i.e., approaching the middle of their subjective day). It can be reliably predicted from the amount of running in this situation whether or not there will be a subsequent phase-shift. Expression of the immediate early genes c-fos and fosB was examined by immunocytochemistry in the suprachiasmatic nucleus (SCN), the intergeniculate leaflet (IGL) of the thalamus, and the medial pretectal area of hamsters that ran vigorously in the novel wheel and would have phase-shifted. c-Fos was increased, compared to levels in a control group left in their home cages, in the IGL, and the pretectum (PT), but decreased in the SCN. No significant changes in FosB were detected in any region examined. An additional experiment argued against the possibility that the changes in c-Fos could be attributed to a rapid advance of the pacemaker to a different phase in the circadian cycle. Counts of c-Fos-positive cells in the IGL were similar in animals given pulses of running starting at CT 4.5 and starting at CT 12.5-16 (i.e., in the subjective night when they would have been active anyway). Altogether the results support the view that activation of the IGL is important in nonphotic clock resetting, and raise the possibility that the PT may also be involved in nonphotic resetting. However, the results also indicate that novelty-induced running does not alter c-Fos induction in a phase-specific manner in the IGL. The inhibition of c-Fos in the SCN by nonphotic phase-shifting events contrasts with the well-known inducing effects of light pulses. These different effects might underlie some of the interactions between nonphotic and photic zeitgebers when both act together on the circadian system.     

Nature’s clocks and human mood: The circadian system modulates reward motivation.

Existing literature on reward motivation pays scant attention to the fact that reward potential of the environment varies dramatically with the light/dark cycle. Evolution, by contrast, treats this fact very seriously: In all species, the circadian system is adapted to optimize the daily rhythm of environmental engagement. We used 3 standard protocols to demonstrate that human reward motivation, as measured in the dynamics of positive affect (PA), is modulated endogenously by the circadian clock. Under naturalistic conditions, 13.0% of PA variance was explained by a 24-hr sinusoid. In a constant routine protocol, 25.0% of PA variance was explained by the unmasked circadian rhythm in core body temperature (CBT). A forced desynchrony study showed PA to align with CBT in exhibiting circadian periodicity independent of a 28-hr sleep/wake cycle. It is concluded that the circadian system modulates reward activation, and implications for models of normal and abnormal mood are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Entrainment of the circadian system of mammals by nonphotic cues

Although light is the principal zeitgeber to the mammalian circadian system, other cues can be shown to have a potent resetting effect on the clock of both adult and perinatal mammals. Nonphotic entrainment may have both biological and therapeutic significance. This review focuses on the effect of behavioral arousal as a nonphotic cue and the neurochemical circuitry that mediates arousal-induced entrainment in the adult rodent. In addition, it considers the role of nonphotic entrainment of the developing circadian system in perinatal life prior to the establishment of retinal input to the clock.     

Reactivation treatment prevents the memory-impairing effects of scopolamine in preweanling rats.

The authors report that the expression of a conditioned odor aversion is impaired in preweanling rats when they are conditioned on Postnatal Day 12 and tested under the influence of scopolamine hydrobromide (0.2 or 0.5 mg/kg, intraperitoneal) after a 48-hr, but not after a 2-hr, retention interval (Experiment 1). This effect of scopolamine is not dependent on maturation of the cholinergic system between Days 12 and 14 (Experiment 2), nor is it due to peripheral mechanisms (Experiment 3). When pups are reexposed to the unconditioned stimulus (footshock) before drug administration, performance on the 48-hr retention test is not impaired by scopolamine (Experiment 4). These findings demonstrate that the cholinergic system may be critical for the retrieval and expression of long-term or weak memories in young rats. However, the expression of active memories (recent or recently reactivated) may not be dependent on the cholinergic system to the same extent as is the expression of inactive memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Olfactory bulbectomy impedes social but not photic reentrainment of circadian rhythms in female Octodon degus

Recent studies demonstrated that nonphotic (social) cues markedly accelerate reentrainment to large phase shifts of the light-dark (LD) cycles in female Octodon degus and that such changes are likely effected by chemosensory stimuli. This experiment investigated the effects of olfactory bulbectomies on (1) socially facilitated reentrainment rates of circadian rhythms following a 6-h phase advance of the LD cycle, (2) photic reentrainment rates of circadian rhythms following a 6-h advance of the LD cycle, (3) photic entrainment, and (4) the circadian period (tau) of activity rhythms in constant darkness (DD). olfactory bulbectomies (BX) blocked socially facilitated reentrainment rates but did not alter reentrainment rates of circadian rhythms to photic cues alone. In addition, BX lowered mean daily locomotor activity levels and decreased the amplitude of the activity rhythm in degus housed in entrained (LD 12:12) conditions but did not alter the phase of activity onset or offset, duration (alpha) of activity, or mean daily core body temperature. Bulbectomies also failed to modify tau of free-running activity rhythms. This experiment confirms that the olfactory bulbs and chemosensory cues are necessary for socially facilitated reentrainment. In contrast to their effects in nocturnal rodents, BX do not produce significant circadian photic changes in diurnal degus. This is the first experiment to determine that chemosensory stimuli modulate the circadian system in a diurnal rodent.     

Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement.

Hypothesized that the amygdaloid complex (AC) is involved in the formation of stimulus–reward associations. A series of experiments (1A–2C) directly compared the effects of lesions (produced by injection of the excitotoxin N-methyl-{D}-aspartic acid) on 1-trial appetitive (APP) and 1-trial aversive (AV) learning in rats. Exps 1A and 1B, which used different degrees of reinforcement, showed no effect of lesions on the APP task, whereas acquisition of the AV task was significantly impaired. This impairment depended on the nature of the AV reinforcement used: Impairment was seen when a highly AV stimulus (footshock) was used but not when a less AV stimulus (0.2% quinine solution) was used. Control experiments showed that the effect of lesions was not due to reduced sensitivity to the footshock. In Exp 2, a novel odor conditioning task examined further the effect of AC lesions on acquisition of APP and AV stimulus–reinforcement associations. As in Exp 1, AC lesions impaired learning of the AV association but did not significantly influence the APP association. Although the AC may be involved in some APP rewarded learning, the differential effect of AC lesions on AV rewarded learning suggests a role in learning beyond the formation of stimulus–reinforcement associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Persistent hunger for sodium makes brain stimulation not so sweet: Theoretical comment on Morris et al. (2006).

The rewarding value of a stimulus is not fixed but rather is subjective and can vary with motivational state. M. J. Morris, E. S. Na, A. J. Grippo, and A. K. Johnson (2006) (see record 2006-07279-008) report that generating a prolonged sodium appetite decreases the rewarding value of lateral hypothalamic brain stimulation and sucrose intake. The findings support the idea that a specific motivational state can have strong, nonspecific consequences for reward processing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motivational Control of Second-Order Conditioning.

Two experiments examined the motivational specificity of the associations that support 2nd-order conditioning. In the 1st phase of each experiment rats were exposed to 2 visual conditioned stimuli (CSs) paired with either a saline or food pellet unconditioned stimulus (US) prior to exposure to 2nd-order conditioning using 2 auditory CSs, 1 paired with each visual CS. Rats' motivational state was then shifted prior to a test such that if and only if specific motivational features of the 1st-order training US played a role in the 2nd-order associative structure would responding to the 2nd-order cues shift appropriately with the state change. Even when the US was irrelevant to the training motivational state, shifts in state revealed that it was encoded within the associative structure supporting 2nd-order responding. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned brain-stimulation reward attenuates the acoustic startle reflex in rats.

The acoustic startle reflex (ASR) in rats is attenuated by a light paired with food or, in humans, by "pleasant" pictures. Rats were trained to barpress for lateral hypothalamus (LH) stimulation. ASR amplitudes were then measured at 4 intensities, with or without a light. Control rats that did not receive brain-stimulation reward (BSR) showed initially lower ASR amplitudes than did rats exposed to BSR, but both groups responded similarly with or without light. Next, experimental rats were given BSR in the presence of light but not in its absence. After conditioning, ASR amplitudes were reduced, and ASR thresholds were raised by a mean of 2.6 dB in the light but remained at preconditioning levels without light. No such change was found for control rats or rats with placements outside the LH. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Associative retuning in the thalamic source of input to the amygdala and auditory cortex: Receptive field plasticity in the medial division of the medial geniculate body.

The medial division of the medial geniculate body (MGm) projects to the lateral amygdala and the upper layer of the auditory cortex and develops physiological plasticity rapidly during classical conditioning. The effects of learning on frequency receptive fields (RFs) in the MGm of the guinea pig have been determined. Classical conditioning (tone–footshock), as indexed by rapid development of conditioned bradycardia, produced conditioned stimulus (CS)–frequency specific RF plasticity: increased response at the CS frequency with decreased responses at other frequencies, both immediately and after a 1-hr retention period. Sensitization training produced only general changes in RFs. These findings are considered with reference to both the elicitation of amygdala-mediated, fear-conditioned responses and the mechanism of retrieval of information stored in the auditory cortex during acquisition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Computational and entrainment models of circadian food-anticipatory activity: Evidence from non-24-hr feeding schedules.

Rats anticipate a daily meal, provided that meal onset intervals are within a circadian (22-31 hr) range. Food-anticipatory activity (FAA) has been interpreted as evidence for a food-entrained circadian pacemaker or for a computational process that uses stored representations of pacemaker phase. The models make different predictions concerning the symmetry and history dependence of the circadian limits to FAA. To test those predictions, rats were entrained to 24-hr light-dark and feeding cycles and then exposed to feeding cycles of 21, 22, 25, 26, or 27 hr. Rats showed strong FAA to feeding cycles ≥24 hr, but not to schedules     

Circadian rhythms during gradually delaying and advancing sleep and light schedules

The circadian rhythms of the night shift worker show very little phase shift in response to the daytime sleep and night work schedule. One strategy for producing circadian adaptation may be to use appropriately timed exposure to high-intensity light. We attempted to shift the circadian temperature rhythms of seven normal subjects while they followed a sleep schedule that gradually delayed (2 h per day) until sleep occurred during the daytime, as is customary for workers during the night shift. After 5 days, the sleep schedule was gradually advanced back to baseline. High illuminance light (2 h per day) and the attenuation or avoidance of sunlight were timed to facilitate temperature rhythm phase shifts. In general, the temperature rhythm did not shift along with the sleep-wake schedule, but appeared either to free run or remain entrained to the natural 24-h zeitgebers. This study showed how difficult it can be to shift human circadian rhythms in the field, when subjects are exposed to competing 24-hr zeitgebers.     

Destruction of serotonergic neurons in the median raphe nucleus blocks circadian rhythm phase shifts to triazolam but not to novel wheel access

Systematic treatment of hamsters with triazolam (TRZ) or novel wheel (NW) access will yield PRCs similar to those for neuropeptide Y. Both TRZ and NW access require an intact intergeniculate leaflet (IGL) to modulate circadian rhythm phase. It is commonly suggested that both stimulus types influence rhythm phase response via a mechanism associated with drug-induced or wheel access-associated locomotion. Furthermore, there have been suggestions that one or both of these stimulus conditions require an intact serotonergic system for modulation of rhythm phase. The present study investigated these issues by making serotonin neuron-specific neurotoxic lesions of the median or dorsal raphe nuclei and evaluating phase response of the hamster circadian locomotor rhythm to TRZ treatment or NW access. The expected effect of TRZ injected at CT 6 h on the average phase advance was virtually eliminated by destruction of serotonin neurons in the median, but not the dorsal, raphe nucleus. No control or lesioned animal engaged in substantial wheel running in response to TRZ. By contrast, all median raphe-lesioned hamsters that engaged in substantial amounts of running when given access to a NW had phase shifts comparable to control or dorsal raphe-lesioned animals. The results demonstrate that serotonergic neurons in the median raphe nucleus contribute to the regulation of rhythm phase response to TRZ and that it is unlikely that these neurons are necessary for phase response to NW access. The data further suggest the presence of separate pathways mediating phase response to the two stimulus conditions. These pathways converge on the IGL, a nucleus afferent to the circadian clock, that is necessary for the expression of phase response to each stimulus type.     

Augmentation of the rat's acoustic startle reflex by nonreflexogenic stimuli.

The size of the rat's acoustic startle reflex was augmented by brief acoustic clicks (which did not themselves elicit startle) presented several milliseconds before the reflex-eliciting stimulus (RS). The same clicks presented after the RS gave relatively weak augmentation that was present in the 1st, but not the 2nd, testing session. Brief footshocks set to 75% of each animal's flinch threshold augmented startle when presented both before and after the RS in both testing sessions. Augmentation by a leading footshock increased with shock intensity and also with the intensity of the RS. Augmentation by a trailing footshock increased with shock intensity and also with the intensity of the RS. Reflex size is not fixed at the time of reflex elicitation but can be augmented by a later nonreflexogenic stimulus. Reflex augmentation may be caused by the 2nd member of a stimulus pair discharging elements of the reflex pathway that were partially activated by the 1st. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The circadian variation of urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transpeptidase in clinically healthy cats

The circadian variation of urinary N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) was evaluated in cats. Urine and blood were collected at 4-hr intervals from adult cats (3 males, 9 females) weighing between 2.6 and 5.0 kg. There was no circadian variation in the urine volume, creatinine clearance, creatinine excretion, NAG excretion or gamma-GTP excretion. The average NAG and gamma-GTP indices in the 4-hr urine were similar to those for the 24-hr urine. However, the variance for the 4-hr urine samples was higher than that of 24-hr urine. In conclusion, although 4-hr urine samples can be used to estimate 24-hr urinary enzyme excretion, short-term spot urine samples may cause increased variation in the enzyme index.