Group rearing abolishes hyperdefensiveness induced in weanling rats by lateral septal or medial accumbens lesions but not by medial hypothalamic lesions

Lesions of the medial hypothalamus, medial accumbens, or septum were made in 21- to 25-day-old male hooded rats. Half of the animals in each group were subsequently reared in groups and the other half in isolation. When tested for defensiveness toward the experimenter at 31, 34, and 37 days postoperatively, rats with medial hypothalamic lesions were most hyperdefensive toward the experimenter if reared in isolation but were significantly more defensive than sham-lesioned animals even when reared in groups. Rats with septal lesions were significantly more defensive than sham-lesioned animals only when reared in isolation while rats with medial accumbens lesions were not different from controls whether reared individually or in groups. These results suggest that the medial hypothalamus may have a special importance in determining temperament since the hyperdefensiveness that results from interference with its functioning is resistant to experiential remediation.     

Mouse killing in rats induced by lesions of the medial hypothalamus or medial accumbens: short-term preoperative exposure to a mouse does not suppress the killing

Rats were either exposed or not exposed to a mouse in their living cage for a 48-hr period. At the end of this time a bilateral lesion was made in the medial accumbens region or in the medial hypothalamus. When tested 2 days postoperatively, the killing frequency among rats that had been exposed to mice preoperatively was not significantly lower than that of rats that were not preoperatively exposed. The ineffectiveness of preoperative experience in suppressing the mouse killing induced by medial accumbens and medial hypothalamic lesions is similar to that found previously with dorsal-median raphe lesions and olfactory bulb lesions and is in contrast to the ease with which preoperative experience prevents mouse killing induced by septal lesions and serotonergic lesions induced by 5,7-dihydroxytryptamine.     

Suppression of VMH-lesion-induced reactivity and aggressiveness in the rat by stimulation of lateral septum, but not medial septum or cingulate cortex

Animals made vicious with bilateral ventromedial hypothalamic lesions had bipolar electrodes implanted unilaterally in the lateral septum, medial septum, or cingulate cortex. Four days later, the animals' reactivity and aggressiveness were evaluated 5 min before, during, and 5 min after stimulation at 20 micronA (60 Hz, sine wave). Lateral septal stimulation suppressed reactivity and aggressiveness by almost 80% compared with pre- and poststimulation levels. Stimulation of neither the cingulate cortex nor the medial septum produced a change reliably different from that seen in unstimulated control animals. Further tests with stimulation of the lateral septum at the 20-micronA level showed that neither rewarding self-stimulation nor disruption of ongoing water drinking was produced. These results are congruent with evidence from lesion studies that the lateral septum normally acts to suppress reactivity and aggressiveness in the rat; they do not support previous suggestions that the medial septum is involved in the modulation of these behaviors.     

Autoshaping a leverpress in rats with lateral, medial, or complete septal lesions

Rats with either control operations or lateral, medial, or complete septal lesions received 600 trials of leverpress training using an autoshaping procedure, i.e., food delivery followed a 10 s illuminated lever presentation, or occurred immediately after a leverpress. Rats with complete septal lesions acquired the leverpress faster than controls and had more food-tray entries per minute during the first 100 trials than the other groups. Rats with lateral or medial septal lesions had leverpress and food-tray entries equivalent to controls. The facilitation of autoshaping a leverpress may partially be explained by the general increase in motor reactivity to stimuli found following septal lesions.     

Effects of medial and lateral septal lesions on the partial reinforcement extinction effect at one trial a day

Rats sustained electrolytic lesions of either the medial septal (MS) area (of a kind known to eliminate the hippocampal theta rhythm) or the dorso-lateral septal (LS) area (of a kind known to spare theta) or both (a “total septal”, TS, lesion). They were compared to sham-operated controls in three experiments in the straight alley with food reward on continuous (CRF) or partial (PRF) reinforcement at one trial a day. MS lesions either left the partial reinforcement extinction effect (PREE) unchanged or enhanced it; LS lesions substantially reduced the PREE. The latter effect was due to a fall in resistance to extinction in PRF animals with no change in CRF animals. MS lesions greatly increased resistance to extinction in both CRF and PRF animals in one experiment but increased resistance to extinction only marginally and only in PRF animals in a second experiment. The TS lesion acted like the LS lesion. These results demonstrate a clear double dissociation between the effects of MS and LS lesions, especially in the PRF condition (LS lesions reduce resistance to extinction, MS lesions increase it).     

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.     

Motivational and neuroanatomical specificity of hypodipsia for aversive solutions produced by medial preoptic injury to the rat.

Bilateral medial preoptic lesions in rats dramatically lowered the rejection threshold for quinine-adulterated water but not for food in 24-hr forced-choice tests. The detection threshold for quinine in a two-bottle choice test, however, was unaffected by the medial preoptic lesion. Bilateral septal and lateral preoptic lesions had no effect on any quinine-adulteration tests. The enhanced rejection of quinine-adulterated water in a forced-choice test by medial-preoptic-damaged rats was also observed after 24-hr of water deprivation. Furthermore, the plasma osmolality of medial preoptic rats was significantly elevated above controls after 24-hr of water deprivation. These findings were interpreted as suggesting that a medial preoptic lesion produces a deficit in thirst-motivated behavior.     

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.     

Septal influences on operant responding in the rat.

The afferent and efferent connections of the septum with the hippocampus (fornix) of with the hypothalamus and lower brain stem (medial forebrain bundle) were transected by means of an encephalotome near the point where these pathways enter or leave the septal area. A transection of the fornix that produced minimal direct damage to cellular components of the septum of hippocampus reproduced the effects of large septal lesions on responding in several temporally defined paradigms that involve periods of response suppression (differential reinforcement of low rates, discriminated Sidman avoidance, fixed interval). Transection of the medial forebrain bundle fibers that interconnect the septum with the hypothalamus and lower brain stem did not affect behavior in any of these paradigms. These observations should be veiwed in the context of the results of earlier investigations which demonstrated that transection of the medial forebrain bundle reproduces several other components of the septal lesion syndrome.     

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.     

Place and response learning of rats in a Morris water maze: differential effects of fimbria fornix and medial prefrontal cortex lesions

The question examined in this study is concerned with a possible functional dissociation between the hippocampal formation and the prefrontal cortex in spatial navigation. Wistar rats with hippocampal damage (inflicted by a bilateral lesion of the fimbria fornix), rats with damage to the medial prefrontal cortex, and control-operated rats were examined for their performance in either one of two different spatial tasks in a Morris water maze, a place learning task (requiring a locale system), or a response learning task (requiring a taxon system). Performance of the classical place learning (allocentric) task was found to be impaired in rats with lesions of the fimbria fornix, but not in rats with damage of the medial prefrontal cortex, while the opposite effect was found in the response learning (egocentric) task. These findings are indicative of a double functional dissociation of these two brain regions with respect to the two different forms of spatial navigation. When the place learning task was modified by relocating the platform, the impairment in animals with fimbria fornix lesions was even more pronounced than before, while the performance of animals with medial prefrontal cortex lesions was similar to that of their controls. When the task was again modified by changing the hidden platform for a clearly visible one (visual cue task), the animals with fimbria fornix lesions had, at least initially, shorter latencies than their controls. By contrast, in the animals with medial prefrontal cortex damage this change led to a slight increase in escape latency.     

The effects of lateral, medial, or complete septal lesions on positive conditioned suppression in rats

This study investigated the effects of lateral, medial, or complete septal lesions in rats on lever pressing and US-approach behaviors during the presentation of a light followed by two free food pellets. Ten days after surgery, groups of rats received 20 sessions of a random interval (RI) 60-s schedule of food reinforcement. The positive conditioned suppression paradigm consisted of 20 sessions of a 10-s light paired with free food while the rats were responding on the RI 60-s schedule. All groups of rats significantly suppressed lever pressing during the 10-s light presentation. During the last four sessions of the 10-s light condition, rats with lateral septal lesions had a significant increase in food-tray entries during the light presentation, while the other groups decreased lever pressing without a change in food-tray entries during the 10-s light presentation. Although rats with septal damage generally have difficulty inhibiting responses in a variety of operant situations, rats with lateral, medial, or complete septal lesions showed no impairment in positive conditioned suppression. This study also suggests that when the spatial arrangement of the CS and the type of US were manipulated to minimize sign-tracking and goal-tracking behaviors, emotional reactions during the presentation of the CS must be considered a factor influencing positive conditioned suppression.     

Gastric pathology and feeding deficits induced by hypothalamic damage in rats: effects of lesion type, size, and placement.

Three doses each of cathodal or anodal direct current were delivered to coagulate lateral hypothalamic tissue bilaterally in rats. Increases in hypothalamic tissue damage were associated with more instances of aphagia, greater amounts of glandular, but not rumenal, gastric pathology, and greater weight loss. Both anodal and cathodal lesions produced aphagia and similar amounts of gastric pathology, but anodal lesions also appeared to facilitate weight loss independently of the tissue damage. Extensive chromatolysis surrounding anodal lesion cavities may be importantly related to the postoperative effects. In additional experiments, anodal electrolytic lesions or cortical suction ablations were used to vary the location of neural damage. Fedding deficits and gastric pathology resulted from the destruction of several brain areas. In particular, eating of dry food in the presence of high gastric pathology was observed in rats with lesions ventral and medial to an area in the dorsolateral hypothalamus that was associated with aphagia. When aphagia was accompained by severe gastric pathology, the brain lesions typically encroached extensively on more ventromedial areas. Moreover, aphagia sometimes was observed with only negligible gastric pathology. It is suggested that gastric pathology is not primary to the expression of the aphagia that follows lateral hypothalamic damage.     

Effects of medial preoptic-anterior hypothalamic lesions on development of sociosexual behavior in dogs

Bilateral medial preoptic-anterior hypothalamic lesions in adult male dogs eliminate or impair copulatory behavior and reduce urine-marking responses but do not affect aggressive behavior. The present study examined the emergence of the adult forms of these same male sociosexual behavioral patterns when the lesions are made prior to puberty. The subjects were allowed to interact with male peers during development. Animals with lesions had reduced frequence of juvenile mounting and an almost total absence of male copulatory activity in adulthood. Urine-marking and aggressive behavior in the juvenile and adult periods were not affected by the lesions. The findings reveal a sparing of function with regard to urine-marking but not sexual behavior.     

Effects of d- versus l-amphetamine, food deprivation, and current intensity on self-stimulation of the lateral hypothalamus, substantia nigra, and medial frontal cortex of the rat.

Intracranial sefl-stimulation (ICSS) was studied in rats with chronically implanted lateral hypothalamic, substantia nigra, or medial frontal cortex bipolar electrodes. A comparison of the effects of d- and l-amphetamine on ICSS response rate indicated that the d isomer had a greater facilitatory effect than the l isomer at lateral hypothalamic and substantia nigra electrode sites but that neither isomer significantly affected medial frontal cortex ICSS. d-Amphetamine resulted in a dose-related increase in motor activity, but the same doses of the l isomer resulted in decreased motor activity. Only lateral hypothalamic ICSS response rates increased significantly in response to food deprivation. Increases in current intensity above the level used for amphetamine and food-deprivation testing facilitated lateral hypothalamic and substantia nigra ICSS response rates but did not significantly affect medial frontal cortex response rates. The responsiveness of ICSS at each electrode site appeared to be correlated with the fiber- and cell-body densities of catecholaminergic systems in the brain.     

Effects of lesions of the amygdala, preoptic area, and hypothalamus on estradiol-induced activity in the female rat.

Lesions of the anterior hypothalamic nucleus and the medial preoptic area sharply attenuated enhancement of wheel running by estradiol benzoate in ovariectomized female rats. Lesions of the corticomedial amygdala had no effect on this behavior. The hormonal effects on activity were largely independent of any changes in body weight. Results of this first experiment indicated that the anterior hypothalamic and medial preoptic areas are critically involved in the induction of activity by estradiol. However, this experiment provided no support for suggestions that the corticomedial amygdala inhibits those structures that mediate the estrogenic induction of activity. In the second experiment, food deprivation was used to stimulate activity. Results of this experiment suggested that the reduction in the ability of estradiol to induce activity following anterior hypothalamic and medial preoptic lesions does not reflect a general inability to become more active.     

Evidence for the thalamic targets of the medial hypothalamic defensive system mediating emotional memory to predatory threats

Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats. Anatomical findings suggest that the PMd is in a position to modulate memory processing through a projecting branch to specific thalamic nuclei, i.e., the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv). In the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual responses to predator-related cues) defensive behaviors. During cat exposure, all experimental groups exhibited intense defensive responses with the animals spending most of the time in the home cage displaying freezing behavior. However, during exposure to the environment previously associated with a cat, the animals with combined RE + AMv lesions, and to a lesser degree, animals with single AMv unilateral lesions, but not animals with single RE lesions, presented a reduction of contextual conditioned defensive responses. Overall, the present results provide clear evidence suggesting that the PMd’s main thalamic targets (i.e., the nucleus reuniens and the AMv) seem to be critically involved in the emotional memory processing related to predator cues.     

Septal damage in infant and adult rats: Effects on activity,emotionality, and muricide

Septal lesions produced signs of increased emotionality in the adult rat, the septal syndrome (hyperresponsiveness to handling; in the open field: decreased rearing and ambulation activity, increased defecation, deficient habituation) being more or less complete and more or less marked depending on the age at which the lesion was performed (7 days or 3 months), the extent of the lesion (restricted to the septum or extending to more ventrally located structures) and the environmental conditions in which the animals were reared (in groups or in isolation). All septal lesions provoked a similar and significant increase in the probability of occurrence of mouse-killing behavior, irrespective of age of operation, extent of lesion and kind of rearing environment. In a 24-hour actography starting at 11:30 a.m., the rats septalectomized at adult age were less active than controls during the initial period, while all septals were markedly more active than controls during the night period. Early septal lesions only transiently disrupted weight gain. The results obtained point to complex interactions between the effects of early brain damage and environmental conditions.     

Hyperreactivity, muricide, and intraspecific aggression in the rat produced by infusion of local anesthetic into the lateral septum or surrounding areas

Intracranial infusions of a local anesthetic (lidocaine, 2%) were made bilaterally (4 microliter over 20 min) through permanently implanted cannulas ending in the lateral septum or adjacent areas. Increases in irritability and reactivity to the experimenter, muricide, and intermale aggression were produced by injections into the lateral septum and the region ventral to it. The increases in reactivity and interanimal aggresion occurred in varying degrees and were independent of one another, but intermale aggression occurred only in animals showing muricide. The most effective site for eliciting the entire spectrum of aggressive behaviors was the region ventral to the anterior septum. The region ventral to the posterior septum (medial preoptic area, anterior hypothalamic area, straia terminalis) was unique in that it tended to produce a high incidence of muricide, with only modest increases in reactivity. The lateral septum was moderately effective in producing the entire range of aggressive behaviors. No changes in behavior were noted with infusions into the medial septum or th medial forebrain bundle/lateral preoptic area ventrolateral to the septum. It is suggested that the hyperreactivity and irritability may be relat to hyperdefensiveness and that muricide and intermale aggression are points on a continuum of interanimal aggressiveness.     

Interpersonal variables affecting attributions of defensiveness

Two studies explored interpersonal factors influencing attributions of defensiveness. In Experiment 1, 22 pairs of undergraduate participants interviewed one another regarding their “worst failure.” Participants’ self- and other-attributions of defensiveness following the interview did not differ significantly, indicating the absence of a self-serving bias. In Experiment 2, 48 participants, assigned to one of three conditions, were interviewed by the experimenter about their “worst failure.” Those who received “extremely defensive” ratings from a fictitious psychologist produced significantly higher self-ratings of defensiveness (p<.0001) than did participants who simply completed self-ratings following the interview or who watched a videotape of the interview prior to completing self-ratings of their interview behavior. A new model of psychological defense is presented, which can account for these results.