Hormonal dissociation of limbic lesion effects on shuttle box avoidance in rats.

Rats with septal or hippocampal lesions, relative to normal rats, showed facilitated acquisition of a shuttle box avoidance response. The rats with septal lesions were also highly resistant to extinction compared with normal rats. When the same lesion effects were examined in hypophysectiomized rats, the animals with septal lesions continued to show facilitated performance, and those rats with hippocampal lesions performed no differently than nonoperated control animals. These findings are consistent with the hypothesis that the facilitated avoidance performance found in rats with hippocampal lesions is attributable to lesion-induced changes in hypophyseal activity, but similar changes induced by septal lesions are not.     

Role of pituitary-adrenocortical system in mediating avoidance behavior of rats with septal lesions.

Three experiments examined the hypothesis that the effects of septal lesions and systemic injections of scopolamine on avoidance acquisition could be attributed to the effects of either of these treatments on adrenocorticotropic hormone (ACTH) secretion. Septal lesions and scopolamine facilitated 2-way conditioned avoidance response acquisition, and the lesions retarded passive avoidance acquisition. However, neither the injections of dexamethasone, a synthetic glucocorticoid which inhibited ACTH secretion as did septal lesions, nor injections of ACTH which mimicked the facilitatory effects of scopolamine on basal ACTH secretion, affected avoidance in these paradigms. Thus, the main hypothesis was not supported. The finding that scopolamine did not affect passive avoidance indicates that a cholinergic system may not be involved in mediating the suppressive effects of punishment.     

Sparing of function after infant lesions of selected limbic structures in the rat.

The effects, in adult animals, of limbic lesions produced in infancy were studied in 273 male Wistar rats using weight gain and conditioned emotional response (CER) and conditioned avoidance response (CAR) acquisition as the critical measures. Subjects received bilateral lesions of the amygdala, septum, posteroventral hippocampus (PH), anterodorsal hippocampus (AH), or frontal cortex either as infants (at 10 days of age) or as adults (at 60 days). Normal and anesthetized control groups were also used. Frontal cortical lesions, AH lesions, and anesthetization had no effect on weights or on CER and CAR acquisition. Both infant and adult amygdala and septal lesions significantly disrupted normal weight gain. Adult-accrued amydala and PH lesions significantly retarded CER acquisition, and adult septal and PH lesions significantly facilitated CAR acquisition. Infant-accrued amygdala lesions significantly retarded CER acquisition but had no effect on CAR acquisition. Infant septal lesions significantly facilitated CAR acquisition, and infant PH lesions had no effect on either task. The results were interpreted to mean that the observed task-specific recovery in early-operated animals may have been due to some form of functional reorganization.     

Deficient passive and one-way active avoidance acquisition following medial forebrain bundle lesions in rats.

Cathodal electrolytic lesions of the medial forebrain bundle (MFB) at posterior hypothalamic levels in male hooded rats produced a mild, transient hypodipsia and lowered jump thresholds to footshock. The lesions produced marked deficits in passive avoidance performance in a paradigm that paired discrete, linearly incrementing footshock intensities with contact of a water spout following 48 hr of water deprivation. Intraperitoneal injections of DL-5-hydroxytryptophan (75 mg/kg), the immediate metabolic precursor of serotonin, had no effect on the passive avoidance performance of either experimental or operated control subjects. Lesions of the MFB also resulted in deficient acquisition in a one-trial step-through passive avoidance paradigm not using motivation to drink and caused a severe acquisition deficit in a one-way active avoidance task. Lesions of the septal nuclei produced lowered jump thresholds but did not affect acquisition in the first passive avoidance task. The results are interpreted as indicating a lesion-induced deficiency in fear learning, independent of the serotonergic functions of the MFB.     

The GM1 ganglioside hastens the reduction of hyperemotionality after septal lesions

The purpose of the present study was to assess the effects of ganglioside treatment on changes in emotional, activity, and avoidance behaviors following septal brain damage. Rats were treated with GM1-gangliosides either before and after septal lesions, or only after septal lesions and tested for emotionality on 10 consecutive days beginning on the second day after surgery. The ganglioside treatment decreased the emotionality of rats with septal damage on the first test day, and enhanced their rate of recovery to control levels of emotionality. Septal rats treated with gangliosides had activity, rearing, and avoidance behaviors equivalent to nontreated septal rats; however, lesioned rats treated with GM1 showed reduced intertrial crossings during avoidance conditioning. These results suggest that the changes in emotional behavior of septal rats treated with GM1 occur shortly after the lesion.     

Behavioral effects of neurotoxic lesions of the ascending monoamine pathways in the rat brain

Intracranial microinjections of 6-hydroxydopamine or 5,6-dihydroxytryptamine into six ascending monoamine pathways produced the expected patterns of depletion of telencephalic serotonin, dopamine, and norepinephrine. Serotonin level was specifically lowered after dorsal or median raphe lesions but not after mesolimbic or nigrostriatal system lesions which lowered both norepinephrine and dopamine. Lesions in the locus coeruleus or ventral nor-adrenergic bundle lowered only norepinephrine, and locus coeruleus lesions elevated serotonin level. Behavior was examined in an open field, one-way active avoidance, and two passive avoidance tasks, and measures were taken of water consumption and body weight. Dorsal raphe lesions had no effect on any of the measures; the other five lesion groups exhibited deficient acquisition of the one-way active avoidance task. In the appetitive passive avoidance task, only the substantia nigra lesion group exhibited a deficiency. In the step-through passive avoidance task, both the substantia nigra and the median raphe groups exhibited a deficit, with the median raphe group exhibiting hyperactivity in the start box during testing. Water consumption was decreased by lesions in the ventral noradrenergic bundle during the first postoperative week and was increased in the median raphe group by the fourth postoperative week. Lastly, lesions in the locus coeruleus dramatically decreased activity in the open field. The results are discussed in regard to the search for specificity of behavioral functions of the distinct ascending monoamine pathways.     

Effects of medial and lateral septal lesions on the partial reinforcement extinction effect at short inter-trial intervals

Rats sustained electrolytic lesions either in the medial septal (MS) area (of a kind known to eliminate the hippocampal theta rhythm) or in the dorso-lateral septal (LS) area (of a kind known to spare theta) and were compared to sham-operated controls in three experiments in the straight alley with food reward on continuous (CRF) or partial (PRF) reinforcement and inter-trial intervals of 3-8 min. With 6 acquisition trials MS lesions increased resistance to extinction and enhanced the partial reinforcement extinction effect (PREE). With 48 acquisition trials MS lesions did not alter resistance to extinction after either CRF or PRF training, but LS lesions abolished the PREE by increasing resistance to extinction in rats trained with CRF and decreasing it in rats trained with PRF. With 96 acquisition trials LS lesions were without effect on resistance to extinction after either CRF or PRF training, as previously reported by Henke (1974) using total septal lesions. Thus the impairment in the PREE previously shown after large septal lesions is due to damage to the lateral, not the medial, septal area.     

Long-term effects of preoptic area knife cuts on the maternal behavior of postpartum rats

Knife cuts severing the lateral connections of the medial preoptic area disrupt maternal behavior in postpartum rats. In these studies the knife cuts were produced 1-2 days prior to behavioral testing. The present study examined whether preoptic area knife cuts produce long-term deficits in maternal behavior. Nulliparous Charles River CD rats received knife cuts severing the lateral connections of the medial preoptic area or sham cuts. Approximately 2 weeks later they were mated. All females delivered young 22-23 days after mating, and litter size did not differ between the groups. Females with preoptic knife cuts cleaned their young, built nests (albeit of inferior quality), crouched over their young in a nursing posture, and lactated. The major deficit shown was the near total elimination of retrieval behavior. Females with preoptic knife cuts, however, were capable of performing the oral-motor responses associated with hoarding behavior. These results show that severing the lateral connections of the medial preoptic area does produce long-term deficits in maternal behavior, particularly with respect to maternal retrieving.     

Perseverative effects of parabrachial lesions: a mechanism of reduced activation?

The acquisition of a spatial reversal task and two reversals of it and the acquisition of an active two-way avoidance task were tested in three groups of male Sprague-Dawley rats: two experimental and one control group. The experimental group received chemical lesions of the parabrachial nuclei (group NPB) or of the dorsal hippocampus (group HC), using ibotenic acid. (Ibotenic acid is a compound which, contrary to kainic acid, fails to produce distant lesions, but, in conformity with kainic acid, spares the majority if not all fibers of passage.) The control group (group CG) received injections of the vehicle solution only. Animals of group NPB, in comparison to those of the other two groups, acquired the reversal task more quickly, but in the acquisition of its two reversals they needed considerably more time and made more perseverative errors. Likewise, only group NPB was significantly impaired in the acquisition of the avoidance task. From these results and from available evidence on connections of the parabrachial neurons with regions specifically involved in variables of the tested tasks (such as the prefrontal cortex), it is concluded that the parabrachial region exerts an activating influence on forebrain areas.     

Interactive effects of training condition and septal lesions on perseverative responding in the rat.

Rats that had received septal lesions either prior to acquisition of a position habit (Group SAR) or immediately after position habit acquisition (Group SR) were tested on two reversals of the task. Compared with control-operated rats, both groups of rats with septal lesions exhibited position-habit reversal deficits. The two groups with septal lesions could not be distinguished in terms of the total number of errors made during reversal learning, but could be distinguished on the basis of the type of error committed. Compared with Group SR, Group SAR made significantly more perservative errors on the first reversal and significantly fewer perserverative errors on the second reversal. Group SR made significantly more nonperservative errors than Group SAR on both reversals.     

Nimodipine accelerates recovery from the hyperemotionality produced by septal lesions

Rats with large electrolytic lesions of the septal area were given the calcium channel antagonist nimodipine (70 micrograms/kg, ip) or its vehicle on the day of surgery and for 3 subsequent days. They were tested for emotionality and compared to control rats for 10 days beginning on the third day after surgery. Forty days after surgery all animals were trained in a two-way active avoidance task for 120 trials. Nimodipine reduced the hyperemotionality found after septal lesions as early as the first test day, and increased the rate of recovery toward control levels on subsequent days. Both septal-lesion groups exhibited more avoidance responses than controls, even though the intertrial crossings were enhanced only in rats with septal lesions that did not receive nimodipine.     

An ACTH4-9 analog (ORG 2766) speeds recovery from septal hyperemotionality in the rat

The amount of hyperemotionality initially demonstrated after septal area lesions was reduced, and the rate at which the hyperemotionality attenuated over repeated testing, was enhanced by the administration of an ACTH4-9 analog, ORG 2766. This ACTH fragment was given for 4 consecutive days after surgery but terminated before testing began. Two weeks after the daily tests of emotionality, the animals were trained in a two-way active avoidance task. The typical increase in avoidance behavior seen in animals with septal lesions was observed in the lesioned animals tested with ORG 2766, but the usual high number of intertrial responses was greatly reduced in these animals. The results indicate that even after a brief series of ORG 2766 administration, there are changes in emotionality that may last for an extended period of time after the cessation of treatment.     

Effects of intrahippocampal injections of the cholinergic neurotoxin AF64A on open-field activity and avoidance learning in the rat

The effects of direct intrahippocampal administration of the cholinergic neurotoxin, AF64A, were investigated in male rats. Bilateral injections of AF64A (5 nmole/2 microliters) produced a significant decrease in choline acetyltransferase (CAT) activity in the dorsal hippocampus (25%) and overlying frontoparietal cortex (30%) but no changes in the striatum. Rats lesioned with AF64A exhibited increased levels of open-field activity, which was most marked at 1 week after the lesion; however, the rates of intrasession habituation were similar in lesioned and control rats. Lesioned rats also displayed deficits in acquisition and retention of a passive avoidance task and less dramatic deficits in acquisition of two-way shuttle box avoidance. These findings indicate that lesioning of cholinergic terminals in the hippocampus and/or cerebral cortex with AF64A leads to long-term deficits in learning and memory as well as increases in open-field activity.     

Cerebellar lesions abolish an avoidance response in rabbit

Unilateral lesions of the cerebellar dentate-interpositus (DI) nuclei abolished or impaired the reacquisition of a nictitating membrane (NM) conditioned avoidance response (CAR) in rabbits. Animals that sustained damage to the DI nuclei and surrounding areas displayed little or no reacquisition of the NM-CAR ipsilateral to the lesion, but displayed excellent acquisition of the response when training was shifted to the contralateral eye. These results agree with previous investigations of the effects of cerebellar lesions on the classically conditioned NM and leg-flexion responses. The DI nuclei appear to be essential for the retention of conditioned responses in a variety of associative paradigms.     

The septum: neural systems involved in eating, drinking, irritability, nuricide, copulation, and activity in rats.

Eating, drinking, irritability, muricide, and copulation were measured in 45 male rats before and after one of three coronal knife cuts in the septal region or a control operation; in addition, activity was measured postoperatively. (a) Cuts posteroventral to the septum resulted in slight hypophagia, marked hyperdipsia, irritability, asexuality, and decrease in activity. (b) Cuts of the fornix resulted only in slight decrease in activity. (c) Cuts through the anterior septum resulted in irritability, slight hyposexuality, and slight decrease in activity. No significant correlations between the various behavioral effects were found. It was suggested that the neural pathways mediating eating, drinking, irritability, muricide, copulation, and activity are relatively distinct and that neural activity in the septal region probably does not influence behavior in any unitary fashion.     

Effects of naloxone on acquisition and extinction of jump-up avoidance behavior in rats

Two experiments were carried out to assess the effects of the opioid antagonist, naloxone, on the acquisition and extinction of shock avoidance by rats in the jump-up apparatus. In Experiment 1 naloxone pretreatment facilitated acquisition but had no effect on extinction of avoidance behavior. In the second experiment the effect of naloxone on acquisition was replicated and in addition, it was shown that naloxone enhanced freezing when a response prevention or flooding procedure was introduced. Again naloxone failed to alter the course of extinction, nor did it interact with the effects of flooding which, by itself, facilitated extinction. The results suggest that naloxone's effects are limited to increasing the functional intensity of the US, and provide further support for the dissociation between extinction of avoidance behavior and other indices of fear.     

Transection of direct anterior thalamic afferents from the hippocampus: effects on activity and active avoidance in rats

This investigation demonstrates the importance of the direct hippocampo-anterior thalamic component of the postcommissural fornix in the control of general locomotion and active avoidance. Transection of anterior thalamic afferents from the hippocampal formation (subicular cortex), at the point where they exit from the fornix posterior to the septum, is sufficient to enhance bidirectional active avoidance acquisition and increase general activity. This transection may also interrupt fibers to or from other thalamic nuclei and the anterior septum. However, destruction of connections of the anterior septum with the hippocampus, habenula, and thalamus by transection in the coronal plane anterior to the descending fornix columns, without damage to the subiculothalamic fibers, increases general activity levels without damage to the subiculothalamic fibers, increases general activity levels without affecting active avoidance behavior. The activity increase in this case resembles that seen after septal lesions rather than that seen after hippocampal lesions. Thus, destruction of a single fornix component contributing afferents to the anterior thalamic nuclei reproduces at least part of the hippocampal syndrome. This suggests that these fibers contribute significantly to the control of these behaviors and may mediate active avoidance changes resulting from hippocampal and fornix damage.     

Proactive behavioral effects of theta-blocking septal stimulation in the rat

The induction of hippocampal theta rhythm using low-frequency septal stimulation has been shown to proactively (1) facilitate the acquisition and (2) increase resistance to extinction of a food-rewarded fixed-ratio (FR) bar-press response (Holt & Gray, Quarterly Journal of Experimental Psychology, 35B, 97-118, 1983). Both (1) and (2) are also seen after septal lesions. This suggests that Holt and Gray's (1983) results may have been due either to stimulation-produced theta waves (the "theta" hypothesis), or a small septal lesion produced by the stimulating current (the "lesion" hypothesis). Both hypotheses were tested in the present experiment using high-frequency septal stimulation. In one of two treatment conditions male Sprague-Dawley rats, chronically implanted with a bilateral septal stimulating electrode and a unilateral bipolar hippocampal recording electrode, received (1) trains of continuous pulses at 77 Hz which blocked the hippocampal theta rhythm, or (2) trains of pulses at 100 Hz interrupted by a 30-msec interval at a frequency of 7.7 Hz. Control animals were implanted but not stimulated. Acquisition of a discrete-trial bar-press response on a fixed ratio 5 reinforcement schedule immediately followed the treatment phase. After 15 days' acquisition all animals were extinguished over the subsequent 12 days. Results indicated that both types of septal stimulation reduced resistance to extinction of barpressing; theta-blocking stimulation produced the greater effect. Theta-blocking stimulation retarded the acquisition of bar-pressing in the early stages of training. These overall results are exactly opposite to those produced by low-frequency (7.7 Hz) theta-driving septal stimulation (Holt & Gray, 1983) and contrary to the predictions of the lesion hypothesis. Furthermore, these findings support the idea that long-term changes in behavior may depend on stimulation-produced changes in the hippocampal theta rhythm.     

The effect of training procedures on fixed-interval responding following septal lesions in rats

Two experiments were conducted to assess the effects of training procedures on fixed-interval (FI) performance of rats with septal lesions. In Experiment 1, rats with septal lesions that had extensive preoperative FI experience responded at higher rates than did control rats in early periods of the FI and at lower rates during the later period of the FI for the first 10 sessions after surgery. Their subsequent FI behavior became equivalent to that of control rats. In Experiment 2, septal rats that were trained on an FI schedule of reinforcement entirely after surgery by gradually increasing the FI requirements had FI performance equivalent to that of rats with control operations. The results suggest that septal lesions result in a transient disruption in the FI performance of rats with previous FI experience without affecting the acquisition of appropriate FI behavior.     

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.