Behavioral and biochemical effects of various food-restriction regimens in the rats

In this paper we describe the effects of six different food restriction (FR) regimens on amphetamine (AMPH)-induced locomotor and nonlocomotor activities in male rats. Changes in serum corticosterone (CORT), insulin and glucose levels were also examined. Each regimen was implemented through different daily food allowance (50%, 25% and 12.5% of the daily food intake, referred to as 50%, 75% and 87.5% FR groups, respectively) and by a specific feeding regimen - either every day (ED) or every other day (EOD). AMPH injection led to a significant increase of locomotor activity in all rats subjected to FR compared to ad libitum fed rats. A significant increase of nonlocomotor activity was observed only in the 75% FR and 87.5% FR groups. The serum CORT levels were significantly elevated and the serum insulin and glucose levels were significantly decreased in all of the FR groups in comparison to the AL rats. The results presented in this paper suggest that the ED regimens produced changes in motor activity and biochemical parameters, which were more-or-less dependent on the degree of FR. In contrast, the EOD regimens induced very similar changes irrespective of the degree of FR degree. Our data support the possible mechanistic roles of CORT and insulin in the effect of FR on locomotor activity, since the most pronounced increase of serum CORT and more pronounced decrease in serum insulin concentration was observed in the groups that also exhibited the highest locomotor activities.     

D-amphetamine enhances skilled reaching after ischemic cortical lesions in rats

Unilateral sensorimotor cortical (SMC) lesions in rats impair reaching and grasping movements of the contralateral forelimb. These impairments can be improved using motor rehabilitative training on a skilled reaching task, but the training may be far from sufficient to return animals to pre-lesion levels of performance. Because D-amphetamine (AMPH) has been found to promote neuroplastic responses to injury and to be very beneficial when combined with some (but not all) types of rehabilitative training, we asked in this experiment whether it could improve the efficacy of rehabilitative training in skilled reaching. Ten to 14 days after unilateral ischemic (endothelin-1 induced) lesions of the SMC, adult rats were given a 3-week regimen of AMPH (1mg/kg) coupled with daily rehabilitative training on a skilled reaching task, the single pellet retrieval task. AMPH treatment not only dramatically improved reaching performance compared with saline-injected controls, the AMPH treated rats surpassed pre-lesion levels of performance by the end of the rehabilitative training period. The greater performance in AMPH compared to saline-treated rats was still evident at 1 month, but not at 2 and 3 months, after the end of rehabilitative training. Thus, AMPH treatment can greatly enhance the efficacy of rehabilitative training on a skilled reaching task after unilateral SMC lesions, but alternate injection and training regimes may be needed to produce permanent improvements.     

Effects of single and group housing conditions and alterations in social and physical contexts on amphetamine-induced behavioral sensitization in rats

Repeated administration of amphetamine (AMPH) can produce behavioral sensitization. However, whether contextual elements and housing conditions influence AMPH-induced behavioral sensitization remains uncertain. This study was designed to examine the effects of housing conditions (single- vs. group-housed) and different contextual changes, including social (with two other co-drug partners) and physical (novel box) context changes, on AMPH-induced behavioral sensitization. During the training phase, all rats were exposed for 7 days to AMPH (1 mg/kg, intraperitoneally) in a Locometer chamber, with the exception of animals tested for the effects of physical context changes trained in a novel box. Following a 7-day withdrawal phase, all rats received an AMPH (0.5 mg/kg) challenge, and locomotor activity in a Locometer box was recorded before and after AMPH injection during the testing phase. Under group housing conditions, animals exposed to a different physical environment between the training and testing phases or accompanying co-drug partners during the training phase exhibited decreased AMPH-induced locomotor sensitization. In contrast, single housing conditions did not have an inhibitory effect on AMPH-induced behavioral sensitization after manipulations of the physical and social contexts. These results suggest that under group housing conditions, both physical and social context changes can attenuate AMPH-induced behavioral sensitization. The possible neural mechanisms underlying the involvement of different housing conditions in AMPH-induced behavioral sensitization are discussed.     

A chronic stress state in rats: effects of repeated stress on basal corticosterone and behavior.

The chronic stress state has previously been defined as persistent visceral arousal coupled with behavioral abnormalities. To determine the number of stressor exposures necessary to induce a chronic stress state, male rats were given 2 hours of inescapable shock on 10, 7, 4, or 3 consecutive days. The 3-day stress group had the most pervasive changes in the variables measured: persistently elevated basal plasma corticosterone (CORT), continued weight loss in the post-stressor period, and abnormal behavior. More exposures to the stress regimen did not produce higher CORT levels or greater behavioral changes. Acutely stressed rats, exposed to 1 day of inescapable shock, had persistent CORT elevations without the other changes seen in the 3-day stress group. The data suggest that 3 days of our stress regimen are sufficient to produce a state of chronic stress and that some signs of this state begin to appear as early as the first exposure to our inescapable stress regimen.     

Enhancement of amphetamine-induced locomotor response in rats on different regimens of diet restriction and 2-deoxy-D-glucose treatment

Diet restriction (DR) in rodents increases lifespan, reduces age-related disease and pathology, increases stress responses, and maintains better function later into life compared with conventional ad libitum (AL) feeding. We have been investigating different DR regimens and also DR mimetics that stimulate stress response pathways that are activated by DR. By inhibiting glycolysis, feeding or injection of 2-deoxy-D-glucose (2DG) has been proposed as a DR mimetic and has been shown to provide neuroprotection. In the current study, we examined whether 2DG treatment produces behavioral changes similar to those observed in DR rats following stimulation of the dopaminergic (DA) system by D-amphetamine (AMPH). Male Fischer 344 rats were maintained on different dietary regimens: 40% daily DR (40% DR); every-other-day feeding (EOD); or AL with some groups provided food containing 0.4% 2DG or injected i.p. with 2DG. In addition, we examined the persistence of effects of DR or 2DG feeding after switching rats to AL. When locomotor activity was assessed at different time points following initiation of dietary treatments, we noted that the enhancement of AMPH-induced locomotor responses emerged earlier in DR rats than observed in 2DG fed rats, but 40% DR and EOD rats responded in a similar manner. Enhanced locomotor responses persisted in 2DG fed rats even when returned to normal diet for 1 month and in the case of DR rats even after 2 months of AL feeding. Three weeks of 2DG injections also enhanced AMPH response, but this effect was transient. The most important finding was that 2DG did not affect body weight or diet intake yet had effects similar to DR. Thus, 2DG appears to activate DA pathways in the same direction as DR does but without the necessity of reducing caloric intake.     

Life-long dietary restriction affects striatally-mediated behavioral responses in aged rats

The effects of life-long dietary restriction on rotational behavior and stereotypy induced by intrastriatally administered dopamine-excitatory (dopamine, DA; amphetamine, AMPH) or cholinergic inhibitory (atropine, AT) agents were examined in rats. Three groups of male Wistar rats were used; mature ad lib (YAL, 6 month), old ad lib (OAL 24 month), and old restricted animals (OR). OR animals were fed and fasted on alternate days from weaning. Each rat was unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine and a cannula was implanted in the right caudate nucleus. Several doses of each drug [AT (0, 1, 7, micrograms) DA (0, 5, 50 micrograms), and AMPH (0, 2, 5, 5, 10 micrograms)] were given randomly (1 dose/day with 1 week between drugs). All doses of a particular drug were given before the next drug regimen was started. A combination of AMPH (25 micrograms) and AT (1 microgram) was also administered in one injection at the completion of all other regimens. Results showed that OR animals responded as well as YAL animals and far better than OAL animals following AMPH, DA, or low doses of AT. However, both the high dose of AT and the combined dose of AMPH-AT seemed to suppress responding in OR animals. Neither AT alone or AMPH-AT combinations had effects in OAL animals. Results are discussed in terms of the possible specificity of effects of dietary restriction on striatal functioning and behavior in senescence.     

Age-related differences in MK-801- and amphetamine-induced locomotor and stereotypic activities of rats

Changes in locomotor and stereotypic activities induced by an i.p. injection of either (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cycloheptan-5,10-imine maleate (dizocilpine or MK-801; 0.3 mg/kg) or D-amphetamine sulfate (AMPH; 1.5 mg/kg) were studied in male Mill Hill hooded rats of different age. The following age groups of animals were considered: 28-30 postnatal day (PND)-old rats (peripubertal), 48-50 PND-old (pubertal), 3-month-old (adults), 12-month-old (middle-aged) and 24-month-old (aged). The motor response was measured by an automated animal activity measuring system. The obtained results showed that: (1) in contrast to AMPH, MK-801 induced more pronounced increases of both locomotor and stereotypic activities in peripubertal and pubertal than in adult and aged rats; (2) AMPH induced the same locomotor and stereotypic activity increase in pubertal, adult and middle-aged rats; (3) both AMPH and MK-801 led to a senescence-related decrease of motor activity. These data suggest that the balance of the glutamatergic and dopaminergic systems changes during aging. Such a change is important in understanding schizophrenia and the motor system decline observed in the later stages of life.     

Food restriction induces long-lasting recovery of spatial memory deficits following global ischemia in delayed matching and non-matching-to-sample radial arm maze tasks

Food restriction has been shown to be beneficial for a number of brain processes. In the current study, we characterized the impact of food restriction on hippocampal damage 70 days following ischemia. We assessed memory and cognitive flexibility of ad libitum fed (AL) and food-restricted (FR) animals using complex delayed non-matching- and matching-to-sample tasks in the radial arm maze. Our findings demonstrate that food restriction led to significant improvement of ischemia-induced memory impairments. FR ischemic animals rapidly reached comparable performance as both AL and FR sham animals in delayed-non-matching (win-shift) and matching (win-stay) radial arm maze tasks. They also made considerably fewer microchoices in the retention trials than AL ischemic animals. In contrast, AL ischemic rats showed persistent spatial memory impairments in the same paradigms. Assessment of basal and stress-induced corticosterone (CORT) secretion revealed no significant differences in baseline levels in AL and FR rats prior to or following global ischemia. However, FR animals showed a more pronounced attenuation of CORT secretion 45 min following restraint. Both FR and AL ischemic rats had comparable cell loss within CA1 and CA3 subfields of Ammon's horn (CA1 and CA3) at 70 days following reperfusion, although a trend toward increased CA3 cell survival was observed in FR ischemic rats. The functional sparing in the FR ischemic animals in the face of equivalent hippocampal cell loss suggests that food restriction somehow enhanced the efficacy of remaining hippocampal or extrahippocampal neurons following ischemia. In the current study, this phenomenon was not associated with diet- and or ischemia-related alterations of vesicular glutamate transporter 1 expression in various hippocampal regions although lower vesicular GABA transporter immunostaining was present in the CA1 stratum oriens and the CA3 stratum radiatum in FR sham and ischemic rats.     

Aging increases basal but not stress-induced levels of corticosterone in the brain of the awake rat

The main purpose of this study was to evaluate the effect of aging on plasma and free corticosterone (CORT) levels in the brain in basal conditions and in response to an acute stressor. Microdialysis experiments were performed in the hippocampus (HC) and the prefrontal cortex (PFC) of young adult (6 months) and aged (24 months) male Wistar rats. Basal free levels of CORT in the HC and the PFC were higher in aged animals. Restraint stress increased plasma CORT and free CORT levels in the HC and the PFC both in young and aged animals. However, while the increase of plasma CORT was higher in aged rats compared with young rats, the increases of free CORT in the HC and the PFC were not different between these two groups of rats. These results suggest that the changes produced by aging in the brain may be related to the enhanced basal levels of free CORT and not to the CORT increases in response to stress.     

Feeding and macronutrient selection patterns in rats: adrenalectomy and chronic corticosterone replacement

To analyze further the role of corticosterone (CORT) in the control of feeding behavior, we examined the impact of adrenalectomy (ADX) and chronic CORT implants on the food intake and macronutrient self-selection patterns of adult male rats at different periods of the diurnal cycle. Consistent with a separate study of acute CORT injection in ADX rats (Kumar and Leibowitz, 1988), the present findings indicate that ADX significantly attenuated the rats' daily (24 hr) ingestion of all three macronutrients, namely, protein, carbohydrate and fat. However, food intake in the dark cycle, specifically during the first few hours after dark onset, was significantly more affected (-70%) than feeding in the later dark and light periods (-25%). Moreover, during this early dark time when circulating CORT level normally peaks, ADX appeared to have its strongest suppressive effect on carbohydrate ingestion. Chronic subcutaneous CORT implants in the ADX animals reversed these effects of surgery and generally restored the rats' eating patterns to that of the cholesterol-implanted SHAM animals. These findings suggest that CORT exerts a decisive influence on caloric intake, on the diurnal pattern of feeding, and on appetite for specific macronutrients. The impact of CORT on carbohydrate intake is apparent specifically during the active eating period, particularly at dark onset when endogenous CORT levels normally peak and carbohydrate is exhibited as the preferred macronutrient.     

Characterization of anxiety and habituation profile following global ischemia in rats

The purpose of the current study was to document the behavioral profile of ischemic rats in novel tasks including the elevated plus maze (EPM), the Vogel/conflict model of anxiety and novelty-induced feeding suppression paradigm as well as to further characterize using behavioral monitoring, the response of ischemic animals in existing paradigms such as the open field. Our findings revealed that ischemic animals spent significantly more time and made more entries in the open arm of the EPM as compared to sham animals, two behaviors indicative of decreased anxiety level. This anxiolytic effect appeared restricted to exploratory models of anxiety, as no differences in punished licking rate were observed between groups in the Vogel/conflict test. In the open field, behavioral monitoring revealed transient ischemia-induced hyperactivity, limited to the initial 15 min of a 30 min testing period. Increased activity in ischemic animals was primarily characterized by increased exploration and sniffing behavior with no significant alterations in rearing and grooming frequencies. Finally, using feeding behavior, our findings revealed a comparable rate of habituation to a novel environment in ischemic and sham rats. Taken together, these results suggest that ischemia-induced hyperactivity may involve a disinhibition to explore unfamiliar and/or mildly anxiogenic environments. However, the basis of such hyperactivity and the presence of habituation deficit following ischemia require further study and/or validation.     

A threshold neurotoxic amphetamine exposure inhibits parietal cortex expression of synaptic plasticity-related genes

Compulsive drug abuse has been conceptualized as a behavioral state where behavioral stimuli override normal decision making. Clinical studies of methamphetamine users have detailed decision making changes and imaging studies have found altered metabolism and activation in the parietal cortex. To examine the molecular effects of amphetamine (AMPH) on the parietal cortex, gene expression responses to amphetamine challenge (7.5 mg/kg) were examined in the parietal cortex of rats pretreated for nine days with either saline, non-neurotoxic amphetamine, or neurotoxic AMPH dosing regimens. The neurotoxic AMPH exposure [three doses of 7.5 mg/kg/day AMPH (6 h between doses), for nine days] produced histological signs of neurotoxicity in the parietal cortex while a non-neurotoxic dosing regimen (2.0 mg/kg/day x 3) did not. Neurotoxic AMPH pretreatment resulted in significantly diminished AMPH challenge-induced mRNA increases of activity-regulated cytoskeletal protein (ARC), nerve growth-factor inducible protein A (NGFI-A), and nerve growth-factor inducible protein B (NGFI-B) in the parietal cortex while neither saline pretreatment nor non-neurotoxic AMPH pretreatment did. This effect was specific to these genes as tissue plasminogen activator (t-PA), neuropeptide Y (NPY) and c-jun expression in response to AMPH challenge was unaltered or enhanced by amphetamine pretreatments. In the striatum, there were no differences between saline, neurotoxic AMPH, and non-neurotoxic AMPH pretreatments on ARC, NGFI-A or NGFI-B expression elicited by the AMPH challenge. These data indicate that the responsiveness of synaptic plasticity-related genes is sensitive to disruption specifically in the parietal cortex by threshold neurotoxic AMPH exposures.     

The effects of amphetamine exposure on juvenile rats on the neuronal morphology of the limbic system at prepubertal,pubertal and postpubertal ages

Amphetamines (AMPH) are psychostimulants widely used for therapy as well as for recreational purposes. Previous results of our group showed that AMPH exposure in pregnant rats induces physiological and behavioral changes in the offspring at prepubertal and postpubertal ages. In addition, several reports have shown that AMPH are capable of modifying the morphology of neurons in some regions of the limbic system. These modifications can cause some psychiatric conditions. However, it is still unclear if there are changes to behavioral and morphological levels when low doses of AMPH are administered at a juvenile age. The aim of this study was to assess the effect of AMPH administration (1 mg/kg) in Sprague-Dawley rats (postnatal day, PD21-PD35) on locomotor activity in a novel environment and compare the neuronal morphology of limbic system areas at three different ages: prepubertal (PD 36), pubertal (PD50) and postpubertal (PD 62). We found that AMPH altered locomotor activity in the prepubertal group, but did not have an effect on the other two age groups. The Golgi-Cox staining method was used to describe the neural morphology of five limbic regions: (Layers 3 and 5) the medial prefrontal cortex (mPFC), the dorsal and ventral hippocampus, the nucleus accumbens and the amygdala, showing that AMPH induced changes at pubertal ages in arborization and spine density of these neurons, but interestingly these changes did not persist at postpubertal ages. Our findings suggest that even early-life AMPH exposure does not induce long-term behavioral and morphological changes, however it causes alterations at pubertal ages in the limbic system networks, a stage of life strongly associated with the development of substance abuse behaviors.     

Changes in contractile properties of motor units of the rat medial gastrocnemius muscle after spinal cord transection

The effects of complete transection of the spinal cord at the level of Th9/10 on contractile properties of the motor units (MUs) in the rat medial gastrocnemius (MG) muscle were investigated. Our results indicate that 1 month after injury the contraction time (time-to-peak) and half-relaxation time were prolonged and the maximal tetanic force in most of the MUs in the MG muscle of spinal rats was reduced. The resistance to fatigue also decreased in most of the MUs in the MG of spinal animals. Moreover, the post-tetanic potentiation of twitches in MUs diminished after spinal cord transection. Criteria for the division of MUs into three types, namely slow (S), fast fatigue resistant (FR) and fast fatigable (FF), applied in intact animals, could not be directly used in spinal animals owing to changes in contractile properties of MUs. The 'sag' phenomenon observed in unfused tetani of fast units in intact animals essentially disappeared in spinal rats and it was only detected in few units, at low frequencies of stimulation only. Therefore, the MUs in spinal rats were classified as fast or slow on the basis of an adjusted borderline of 20 ms, instead of 18 ms as in intact animals, owing to a slightly longer contraction time of those fast motor units with the 'sag'. We conclude that all basic contractile properties of rat motor units in the medial gastrocnemius muscle are significantly changed 1 month after complete spinal cord transection, with the majority of motor units being more fatigable and slower than those of intact rats.     

Deficits in cortico-striatal synaptic plasticity and behavioral habituation in rats with portacaval anastomosis

Hepatic encephalopathy is characterized by disturbances of motor and cognitive functions involving the basal ganglia. So far no standards for assessment of neuropsychiatric abnormalities (disorders of sleep, mood, anxiety and personality) in subclinical hepatic encephalopathy have been defined. Using an animal model of mild (subclinical) hepatic encephalopathy we investigated now striatum-related behaviors and cortico-striatal synaptic plasticity in rats 2 months after introduction of a portacaval shunt and sham-operated matched controls. In a novel open field portacaval shunt rats displayed less locomotor activity; unlike controls they also showed no habituation to the field and no recall of the field environment after 24 h, indicative of cognitive deficit. The elevated-plus maze test indicated no differences in fear/anxiety in the portacaval shunt animals. Tetanic stimulation of cortical afferents in magnesium-free solution evoked an N-methyl-D-aspartate-dependent long-term potentiation in sham-operated animals. In portacaval shunt animals long-term potentiation was significantly impaired. Histamine, a potent modulator of cortico-striatal transmission, induced a larger long-term depression of field potentials in control compared with portacaval shunt rats. In conclusion, a combination of electrophysiological and behavioral approaches has revealed functional changes in cortico-striatal transmission. These data are relevant for understanding the mechanisms of motor and cognitive dysfunctions in hepatic encephalopathy patients and for the development of precise psychometric tests, evaluating cognitive deficits in subclinical hepatic encephalopathy.     

Do long-term glucocorticoid treatments induce behavioral rhythm disturbances in rats?

To examine the influences of a long-term glucocorticoid treatment on behavioral rhythm in rats, I measured motor activity, feeding and drinking, and body temperature in rats that had been treated with corticosterone over a long term, by means of an automatic behavioral measurement system combined with a telemetry system. Either a cholesterol (100 mg, as a control) or corticosterone (100 mg) bead was implanted subcutaneously in rats for 3 months, and the effects of the treatments on behavioral parameters were evaluated 2 to 4 months after the termination of the treatments. Corticosterone did not significantly change daily rhythms of all four parameters and mean values of them. However, three out of six corticosterone-treated rats appeared to show higher the mesor of motor activity compared with the control group. The present study demonstrates that a long-term glucocorticoid treatment does not impair behavioral daily rhythm, then suggests that a long-term glucocorticoid exposures could not damage the endogenous clock of the brain, that is, the suprachiasmatic nucleus.     

A single social defeat induces short-lasting behavioral sensitization to amphetamine

Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing potential of a single exposure to stress is not clear. Both drug- and stress-induced sensitization depend on an enhanced dopaminergic neurotransmission in the mesolimbic DA system. Apart from responding to rewards, this system is also involved in responding towards aversive social stimuli. Therefore, social stressors may be particularly effective in inducing cross-sensitization to stimulant drugs. We examined the time course of sensitization to the locomotor effects of the stimulant, AMPH, following a single social stressor: a social defeat. Wistar rats were exposed in a resident-intruder paradigm to an unfamiliar dominant male conspecific (Wild-Type Groningen), resulting in defeat. The locomotor effects of a subsequent AMPH challenge (0.25 or 1.0 mg/kg) were evaluated 3, 14, and 21 days later by scoring horizontal movement in an open field. AMPH had significantly larger locomotor-activating effects in animals that had been defeated 3 days earlier compared to nondefeated controls. However, this sensitized response was no longer present 14 or 21 days after defeat. Therefore, we conclude that social defeat induces short-lasting cross-sensitization to the locomotor effects of AMPH in rats, but is not sufficient for long-term sensitization. The transient enhancement of responses to dopaminergic drugs may be indicative of a temporary role of dopamine in the cascade of physiological and behavioral changes following social defeat.     

Reduction of motor behavioral deficits in senescent animals via chronic prolactin administration. I. Rotational behavior

The effects of chronic prolactin administration on amphetamine or dopamine (DA) induced rotational behavior was examined in mature (6 month) and senescent (24 month) Wistar rats which were unilaterally lesioned in the left substantia nigra with 6-hydroxydopamine. Prolactin (150 ng/hr) was administered for 7 days via subcutaneously implanted Alzet minipumps. Amphetamine (AMPH) (0, 10 micrograms) or DA (0, 25 micrograms) was administered through cannula which had been implanted into the right (intact) striatum. Both DA-active agents were given prior to pump implantation and on day 4 of prolactin administration. The AMPH was dissolved in saline (1 microliter; pH, 5.5-6.0), while DA was dissolved in N2 bubbled distilled H2O (1 microliter; pH, 5.5-6.0) and the animals were pretreated with nialamide (50 mg/kg) intraperitoneally 1 hr before DA or DA-vehicle injection. The order of drug administration was counterbalanced within the age groups. Results showed that both groups of animals exhibited higher rotational behavior scores following prolactin treatment. In fact, there was a trend toward greater enhancement of rotational behavior in the senescent animals following prolactin treatment than that seen in mature animals. These results parallel those reported previously wherein it was found that striatal DA receptor concentrations (as assessed with [3H]spiperone binding) were higher in prolactin treated mature and senescent animals than in their respective controls. The findings suggest that there is a relationship between increases in the density of striatal DA receptors and improvement in motor performance tasks in senescent animals.     

Circadian dependence of corticosterone release to light exposure in the rat

Previous studies have demonstrated a positive correlation between glucocorticoid levels and circadian reentrainment time following a shift in the light:dark (LD) cycle. We conducted a series of experiments to examine the circadian dependence of the corticosterone (CORT) response to light. Exp. 1 measured CORT release in rats exposed to light at six timepoints. Light presented during the subjective night increased CORT (p<0.05), while light presented during the subjective day did not. In Exp. 2, we documented the time course of the CORT response to light in entrained animals. Rats exposed to light at zeitgeber time (ZT) 18 had a maximal increase in CORT levels following 60 min of stimulus presentation (p<0.05). There was also an increase in adrenocorticotropic hormone following 15 min of light at ZT18 (p<0.05). In an effort to elucidate the effect of changes in the LD cycle on the circadian profile of CORT, Exp. 3 followed the CORT rhythm (in cerebrospinal fluid) of rats prior to and following a shift in the LD cycle. The CORT nadir was elevated following a 6 h photic advance (p<0.05), as was the mean CORT concentration during the peak phase (p<0.05). Most components of the circadian CORT rhythm, however, failed to show an immediate shift towards the change in the light cycle. Together, these data support the hypothesis that a photic phase-shift results in elevated CORT levels, while the rhythm of CORT secretion is robust against changes in the photic environment.     

Lack of effects of handling habituation and swimming stress on ethanol-induced motor impairment and GABAA receptor function.

The effects of handling habituation and swimming stress on ethanol-induced motor impairment and the GABAA receptor function were studied in adult male Wistar rats. Daily handling for 3 to 5 weeks had no significant effect on ethanol-induced motor impairment in the tilting plane test or on the activity of the rats in the elevated plus-maze test of anxiety. Plasma corticosterone concentrations were greatly elevated by the tilting plane test procedure, irrespective of handling habituation. Acute, 10-min swimming stress at +25 degrees C produced an elevated plasma corticosterone concentration comparable to that produced by the tilting plane test, again irrespective of handling habituation. In cerebrocortical homogenates, short-term swimming stress had no statistically significant effect on the muscimol stimulation of the GABAA receptor-mediated 36Cl- flux in handled and non-handled animals. Thus, handling habituation and stress had only minor effects on the activity of the central GABAergic systems in acute tests at behavioural and biochemical levels.