Finn Konow Jellestad

Passive avoidance after ibotenic acid and radio frequency lesions in the rat amygdala.

Ibotenic acid (IBO) is assumed to lesion neurons and to spare fibers of passage. The effects of such lesions in the amygdaloid complex of rats were compared to those of radio frequency lesions (RF) on a passive avoidance task. Both lesions impaired the acquisition of the passive avoidance response. Plasma corticosterone levels were measured after a retention test in which no electrical shocks were applied. None of the lesion groups showed reduced corticosterone levels, the IBO lesioned rats actually showed significantly higher corticosterone levels than both RF lesioned and control animals. The corticosterone results are not consistent with a general reduction in fear. The slower avoidance learning may be a conditioning deficit due to impaired sensory information processing in the amygdaloid complex.

Plasma corticosterone and meal expectancy in rats: Effects of low probability cues

The plasma corticosterone levels of rats were examined prior to their morning meal on Days 1, 7 and 20 of a regimen of 1 hr access daily to food mash and water. The relationship between external cues and meal provision was varied by feeding some groups immediately upon room entry each morning, and others with a variable interval 90-min delay. On Day 1, corticosterone levels of the hungry rats were elevated around the time of light onset, and until 90 min following room entry. On Day 7, corticosterone levels increased in response to room entry in the delay-fed rats, but did not increase further in immediately fed rats. These results were interpreted as indicating that low, but nonzero, expectancy of meal availability elevates corticosterone levels. On Day 20, the immediately fed rats showed a dip in corticosterone levels after room entry, responding to cues highly predictive of imminent meal availability. Delay-fed rats no longer showed an elevation to room entry. The relationship between corticosterone level and meal expectancy is essentially curvilinear in the hungry rat. The corticosterone levels are high when there is uncertainty about whether food is coming or not, and low when there is a very high or very low probability that food is coming.

Behavioral effects after ibotenic acid, 6-OHDA and electrolytic lesions in the central amygdala nucleus of the rat

Selective lesions of central amygdaloid neurons with ibotenic acid and electrolytic destruction of the nucleus both led to marked increases in open field activity and activity during passive avoidance conditioning. However, electrolytic lesions of both neurons and fibers resulted in the most pronounced passive avoidance impairments and it is suggested that this lesion effect should be attributed to a combined destruction of intrinsic neurons and neurons located outside the central amygdala nucleus. The 6-OHDA lesions resulted in no significant changes in the behavioral parameters under investigation or in plasma corticosterone levels. The lack of reduced corticosterone levels in any of the lesioned groups do not indicate that general fear arousal is critically dependent on intact central amygdala neurons in the rat. The behavioral data are, however, still compatible with a hypothesis of a temporary reduction in fear arousal during the initial phase of the passive avoidance conditioning.

Early and Later Life Stress Alter Brain Activity and Sleep in Rats

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

Exploration and avoidance learning after ibotenic acid and radio frequency lesions in the rat amygdala

Open-field activity, avoidance behavior, and plasma corticosterone levels were studied after intraamygdala injections of 3.0 micrograms ibotenic acid (IBO) and radio-frequency (RF) lesions in the amygdala complex of male Wistar rats. The experiments were undertaken to evaluate the importance of amygdala neurons versus axons of passage in fear-motivated behavior. The IBO lesions led to increased open-field activity, but no impairments in active avoidance learning, nor changes in basal or experimental levels of plasma corticosterone. The RF lesions, on the other hand, led to an increase in experimental plasma corticosterone levels. In the one-way avoidance task the RF lesions, in contrast to the IBO lesions, led to significant impairments in the acquisition of the avoidance response. Although the long-term axon-sparing effect of IBO is questioned since cavities were detected in the affected areas 8 weeks after the injections, the differences in avoidance learning and in corticosterone levels between the RF and the IBO lesions indicate that the axons were functionally active at the time of testing (14-26 days postoperatively). The increase in open-field activity is attributed to the destruction of amygdala neurons and neurons in the overlying cortex, while an avoidance deficit seem to depend on the destruction of axons. On the basis of the behavioral results and the corticosterone data in these experiments, it is suggested that the behavioral changes are not attributable to a general reduction in the arousal of fear. However, since the IBO lesions did not affect the most medial parts of the amygdala complex including the central amygdala nucleus, the role of this nucleus in fear arousal has to be investigated further.

Subtotal lesions of the amygdala: The rostral central nucleus in passive avoidance and ulceration

Rats received small bilateral electrolytic or ibotenate lesions of the rostral part of the amygdaloid central (rACE) or lateral (rAL) nuclei, or caudal part of the basolateral nuclei (cBL), or electrolytic lesions of the dorsal hippocampus (HIPP). All groups were tested in a drinking passive avoidance (PA) task that appears less sensitive to deficits in acquisition/retention or activity/spatial perception than are many other PA tasks, and more specifically sensitive to deficits in generation of fear. Consistent with this interpretation, performance in the task was facilitated, not deficient, in the HIPP group. Electrolytic lesions of rAL produced a mild deficit in PA, but ibotenate lesions did not, and neither did the more caudal lesions of the cBL groups. Ibotenate lesions of rACE did produce a deficit in PA, consistent with views of a role of this part of the amygdala in fear. Electrolytic lesions of rACE produced a very profound PA deficit and also blocked the rapid development of gastric erosions by water-restraint stress, effects that were not found with ibotenate lesions in this location. This suggests a particular contribution of fibers passing through rACE to some of the more marked effects of electrolytic lesions of rostrodorsal portions of the amygdala.

Long-term effects of footshock and social defeat on anxiety-like behaviours in rats: Relationships to pre-stressor plasma corticosterone concentration

We compared the consequences of two stressors, ‘unnatural’ inescapable footshocks (IFSs) and ‘natural’ social defeat (SD), on behaviours typically sensitive to stress [sucrose preference, open field (OF), elevated plus maze (EPM) and acoustic startle responses (ASRs)] and the association with pre-stressor plasma corticosterone concentration. After initial blood sampling, rats (n = 20 per group) were exposed to either 10 IFSs (1 mA intensity, 5 s duration each) or to 1 h SD (defeat by an aggressive resident male rat and further exposure but separated in a small cage) or to control procedures (handling). Rats were tested once for ASR (day 19), while the other behavioural tests were applied once weekly for 3 weeks. Both stress groups showed short-lasting lowered sucrose preference, and in the EPM they showed shorter total distance moved, shorter distance moved on open arms and less time on open arms compared to controls. In the OF test, IFS rats showed shorter total distance moved up to 2 weeks after stress. The SD group showed shorter total distance moved in the OF, which was only significant 2 weeks after stress. Low pre-stressor plasma corticosterone concentration was only associated with defecation (IFS rats) and latency to enter open arms in the EPM (all low corticosterone subgroups, n = 10 per subgroup). SD rats with high initial plasma corticosterone concentration showed enhanced ASR compared to the other subgroups with high initial plasma corticosterone concentration (n = 9 per subgroup). The results indicate that footshock and SD, while generally leading to an increase in anxiety behaviours, represent qualitatively different stressors.

Electroencephalographic activity after kainic and ibotenic acid injections in the amygdaloid complex of rats

Long-term electroencephalographic (EEG) activity and neuropathological effects were studied after unilateral amygdaloid injections of kainic acid (KA) and ibotenic acid (IBO). Injections of 0.2 microgram KA caused severe epileptiform activity which lasted up to postoperative day 49. Complete losses of neuronal and glial elements appeared as cavities within the injected areas. Epileptiform activity after injections of 3.0 micrograms IBO was seen only as interictal spikes which lasted for 2-4 h after surgery. Cavities within the lesion areas were also evident in the IBO-injected rats. The results suggest that KA should be avoided as a lesion method in behavioral studies of brain functions, whereas IBO is judged to be a more suitable lesion tool, which produces only transitory and negligible epileptiform activity. However, neither KA nor IBO seems to have long-term fiber-sparing properties.

Relating acoustic startle reactivity and plasticity to alcohol consumption in male Wistar rats

The purpose of this study was to investigate the relationship between the startle response and ethanol. Aspects of the startle response, including initial and average startle, habituation, and prepulse inhibition (PPI) were studied. The startle response was measured to detect potential predictors of voluntary ethanol consumption and to observe whether ethanol ingestion would affect startle in subsequent tests. Rats were tested three times in a standard startle chamber. After the initial startle test, rats categorized as showing high or low PPI were allocated in a balanced way to a free-choice ethanol-water regime or to the water-regime control group. At the end of the ethanol period (lasting for 16 days, including access to ethanol for 10 days), the rats were tested again in the startle chamber 24 h after ethanol removal. After 5 weeks of ethanol abstinence, rats were exposed to a final startle test. The response to the first 120-dB stimulus showed an inverted U-shaped, curvilinear relationship to later ethanol consumption. Startle habituation appeared to have predictive value regarding ethanol consumption, with rats showing the most efficient habituation drinking most. Data showed no relationship between PPI and ethanol intake. Rats given access to ethanol showed greater habituation in the post-ethanol test than did the water controls. After 5 weeks of abstinence, low ethanol-consuming rats showed lower startle responses to the first 120-dB stimulus than did high ethanol-consuming rats. The present data suggest a two-way relationship between startle response characteristics and alcohol.

Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations

The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2–14, male Wistar rats (n = 8 per group) were daily separated from their mothers for a period of either 180 min (long maternal separation; LMS) or 10 min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors.