High affinity [3H]imipramine and [3H]paroxetine binding sites in suicide brains

Specific binding of [3H]imipramine and [3H]paroxetine was simultaneously examined in human brains (frontal cortex, temporal cortex, cingulate cortex, hypothalamus, hippocampus and amygdala) from 11 controls and 11 depressed suicide victims. A single saturable high affinity site was obtained for both radioligands. Age was not related to significant changes in [3H]imipramine and [3H]paroxetine binding parameters, which indicates the stability of the brain serotonergic system with increasing age. A major finding of the present study concerns the existence of a significant decrease in the maximum number (Bmax) of [3H]imipramine binding sites in hippocampus from depressed suicides as compared with the control group, without changes in the binding affinity (Kd). In contrast, when [3H]paroxetine was used as radioligand, no changes in either Bmax or Kd were detected in any of the brain regions studied. These findings suggest that [3H]imipramine may be a better marker than [3H]paroxetine when alterations in the presynaptic serotonergic uptake site are to be detected.     

Direct effects of stress on adrenocortical function

The adrenal gland plays a pivotal role in the stress response since this response involves the hypothalamic-pituitary-adrenal axis (HPAA) and the sympatho-adrenomedullary system (SAMS) as its two principal components. An important relation between the immune system and the other stress response systems is also centered on the adrenal gland. It is well known that the cortex secretes glucocorticoids while the medulla secretes epinephrine, two of the major effects of the stress response. Some other aspects, however, also deserve special consideration: The paracrine effects of the cortical secretion on the medullary cells through the special irrigation system of the gland and reciprocally the influence of the medulla upon the cortex, either by direct close contact or by local innervation. The influence of vascular events also needs to be considered as well as the existence of some local hormonal axis such as those resulting from the local production of renin or CRH in adrenal cells. Some other cells such as mast cells, macrophages and endothelial cells seem to play a role in the regulation of the adrenal cortex and hence in the tuning of the stress response. Stressors stimulate the release of CRH from the hypothalamic paraventricular nucleus inducing the secretion of ACTH from the pituitary and that of corticosteroids from the adrenal cortex. Through the activation of the sympathetic system the adrenal can be stimulated even before adequate levels of ACTH are reached. In conditions of chronic stress the adrenal cortex undergoes an adaptation that allows the hypersecretion of glucocorticoids to occur even without the increment of ACTH.     

Regional and temporal separation of serotonergic activity mediating social stress

Stressful aggressive interaction stimulates central serotonergic activation in telencephalon as well as brainstem. Social roles can be distinguished by monoamine activity following aggression. Pairs of male lizards, Anolis carolinensis, were allowed to fight and form dominant/subordinate relationships. In micropunched regions of telencephalon, the greatest serotonergic changes occur in subordinate males. In hippocampal cortex and nucleus accumbens, subordinate males have increased 5-hydroxyindoleacetic acid/serotonin at 1 h following the fight. In these areas the ratio gradually decreases over a week of cohabitation, as was previously reported for brainstem. Medial and lateral amygdala develop increased serotonergic activity more slowly, with the greatest increase being evident following a week of interaction. Turnover, serotonin and 5-hydroxyindoleacetic acid levels in amygdala escalate over the first week of interaction in subordinate males, and return to baseline by one month. In dominant males, the pattern is accelerated, with the most extensive serotonin system activity present at 1 h, then decreasing over a month. The patterns of serotonergic activation are so similar in hippocampus, nucleus accumbens and brainstem that a co-ordinated response may be involved in mediating short-term social stress and aggression. Similarly, medial and lateral amygdala exhibit corresponding, but delayed patterns in subordinate males, suggesting a co-ordinated response in these regions mediating longer-term stress responses. These data are consistent with rapid neuroendocrine stress modulation in dominant individuals, and delayed serotonergic activity changes in subordinate males.     

Regulation of messenger ribonucleic acid for corticotropin releasing hormone receptor in the pituitary during stress

The mechanism regulating pituitary CRH receptors during stress was studied by analysis of the changes in CRH receptor messenger RNA (mRNA) and CRH binding after acute and repeated stress and CRH and vasopressin (VP) administration in intact and adrenalectomized rats. Acute stress caused time- and stress type-dependent changes in pituitary CRH receptor expression. In situ hybridization studies showed biphasic changes in CRH receptor mRNA after immobilization stress for 1 h and decreases by 2 h (P < 0.01). Increases (P < 0.01) were seen 4 and 8 h after the initiation of the stress, and a return to near basal levels by 12 and 18 h. A different pattern, with a decrease by 4 h (P < 0.01) and levels similar to controls after 12 and 18 h, was observed after a single ip injection of hypertonic saline (1.5 M NaCl). Binding autoradiography showed significant increases in pituitary CRH binding 4, 10, and 12 h after immobilization stress, but significant decreases 4, 12, and 18 h after ip hypertonic saline. In contrast, repeated immobilization or ip hypertonic saline for 8 or 14 days increased pituitary CRH receptor mRNA, and CRH binding was decreased. To determine the role of hypothalamic CRH and VP on these stress-induced changes, rats were injected for 14 days with CRH, VP, or their combination at doses mimicking stress levels in pituitary portal circulation (1 microgram/day sc). Repeated injection of CRH or VP increased CRH receptor mRNA and CRH binding (P < 0.05). CRH receptor mRNA levels further increased after combined administration of CRH and VP (P < 0.01), but CRH binding showed a tendency to decrease. The role of glucocorticoids on CRH receptor regulation was studied by analysis of the effects of stress on CRH receptor mRNA and CRH binding in adrenalectomized (ADX) rats with and without corticosterone replacement in the drinking water. Although in 6-day ADX rats pituitary CRH receptor mRNA levels were markedly reduced after acute immobilization, glucocorticoid replacement restored the stimulatory effect of stress to levels observed in intact rats. Similarly, a single sc injection of CRH (1 microgram) decreased CRH receptor mRNA in ADX rats but not in glucocorticoid-replaced ADX rats. CRH binding showed the expected decrease after ADX and was unchanged after stress or CRH injection. The increased pituitary CRH receptor mRNA after stress suggests that stress-induced CRH receptor down-regulation is due to increased receptor occupancy and internalization rather than to a decrease in receptor synthesis. The data suggest that increased hypothalamic secretion of CRH and VP mediates the delayed up-regulatory effect of stress on CRH receptor mRNA, and that resting levels of glucocorticoids are required for this effect. In addition, increased VP levels are permissive for the down-regulation of CRH binding induced by chronic pituitary exposure to stress levels of CRH.     

Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.

Long-Evans hooded rat pups were either handled or undisturbed between birth and weaning on Day 21. Following weaning, half of the Ss in each group were housed socially, and half were housed in isolation. At 120–250 days of age, [–3H]dexamethasone binding was examined. Binding was significantly higher in the hippocampus of handled than nonhandled groups. In the frontal cortex, binding was higher in the handled/socially reared Ss than in isolated Ss. There were no significant handling or housing effects found in the amygdala, hypothalamus, septum, or pituitary. Thus, early postnatal handling appears to influence the development of the glucocorticoid receptor system in the hippocampus and frontal cortex. Results are discussed as providing a possible mechanism for some of the previously reported effects of early handling on the development of the pituitary-adrenal response to stress. (33 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of corticotropin-releasing hormone gene expression by glucocorticoids: implication for understanding the states of fear and anxiety and allostatic load

Evidence supports the idea of two distinct corticotropin-releasing hormone (CRH) systems in the brain: one which is constrained by glucocorticoids and the other which is not. It is this latter system that includes two primary sites (central nucleus of the amygdala and the lateral bed nucleus of the stria terminalis) in which the regulation of CRH gene expression can be disassociated from that of the paraventricular nucleus of the hypothalamus. It is this other system that we think is linked to fear and anxiety and to clinical syndromes (excessively shy fearful children, melancholic depression, post-traumatic stress disorder and self-administration of psychotropic drugs). The excess glucocorticoids and CRH, and the state of anticipatory anxiety, contribute to allostatic load, a new term that refers to the wear and tear on the body and brain arising from attempts to adapt to adversity.     

Immobilization-induced stress activates neuronal nitric oxide synthase (nNOS) mRNA and protein in hypothalamic-pituitary-adrenal axis in rats

The purpose of this study was to determine whether immobilization stress can cause changes in the enzyme activity and gene expression of neuronal nitric oxide synthase (nNOS) in the hypothalamus, pituitary, and adrenal gland in rats. NOS enzyme activity was measured as the rate of [3H]arginine conversion to citrulline, and the level of nNOS mRNA signal was determined using in situ hybridization and image analysis. NOS-positive cells were also visualized using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-diaphorase) histochemistry and by immunohistochemistry using an anti-nNOS antibody. A significant increase of NOS enzyme activity in the anterior pituitary, adrenal cortex, and adrenal medulla (1.5-, 3.5-, and 2.5-fold) was observed in the stressed animals (immobilization of 6 h) as compared to non-stressed control rats. Up-regulation of nNOS mRNA expression in anterior pituitary and adrenal cortex was already detectable after stress for 2 h with 1.5- and 2-fold increase, respectively. The nNOS mRNA signals in hypothalamic paraventricular nucleus (PVN) significantly increased after the stress for 6 h. This increase in NOS enzyme activity was confirmed using NADPH-diaphorase staining and immunostaining in the PVN and adrenal cortex. An increase of NOS enzyme activity in adrenal medulla after immobilization for 6 h posited by far longer than in the adrenal cortex and anterior pituitary. The present findings suggest that psychological and/or physiological stress causes NO release in hypothalamic-pituitary-adrenal (HPA) axis and in sympatho-adrenal system. It is suggested that NO may modulate a stress-induced activation of the HPA axis and the sympatho-adrenal medullary system. The different duration of stress-induced NOS activity in HPA axis and the adrenal medulla may suggest NO synthesis is controlled by separate mechanism in the two HPA and the sympatho-adrenal systems.     

Rapid stress-induced elevations in corticotropin-releasing hormone mRNA in rat central amygdala nucleus and hypothalamic paraventricular nucleus: an in situ hybridization analysis

High densities of nerve cells containing corticotropin-releasing hormone (CRH) are located in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) of the hypothalamus. These brain regions play an important role in activating autonomic, behavioral, and endocrine responses to stress. This study was conducted to provide needed information concerning the acute effects of stress on CeA and PVN CRH mRNA expression. Rats were exposed to restraint stress for 1 h and brains collected after a 1-h post-stress interval. CRH mRNA expression occurring in the CeA and PVN was examined using in situ hybridization techniques. Densitometric analysis revealed that acute restraint stress produced significant increases in CRH mRNA levels in the PVN and in the rostral CeA region. In addition, the area in the rostral CeA encompassing high CRH mRNA signals increased significantly after stress. Results provide clear evidence that CRH neurons in the CeA and PVN exhibit rapid increases in CRH mRNA expression after exposure to stress.     

Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain

Regional differences in the modulation of [3H] muscimol binding to GABAA receptor complexes by kavapyrones, compounds of the rhizome of the plant Piper methysticum which possess sedative activity, were demonstrated using membrane fractions obtained from target brain centers of kavapyrone action: hippocampus (HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers outside the main kavapyrone effects as frontal cortex (FC) and cerebellum (CER). The kava extract enhanced the binding of [3H] muscimol in a concentration-dependent manner with maximal potentiation of 358% over control in HIP followed by AMY and MED (main target brain centers). Minimal stimulation was observed in CER followed by FC. In contrast, apart from CER, the potency of kavapyrones was similar in the brain areas investigated with EC50 values ranging between 200 and 300 microM kavapyrones. Scatchard analysis revealed that the observed effects of kavapyrones were due to an increase in the number of binding sites (Bmax), rather than to a change in affinity. At a kavapyrone concentration of 500 microM the order of enhancement in Bmax was HIP = AMY > MED > FC > CER. When kavapyrones are included together with pentobarbital or HPO the two classes of compounds produced a more than additive, i.e., synergetic effect on [3H] muscimol binding. Our findings suggest that one way kavapyrones might mediate sedative effects in vivo is through effects on GABAA receptor binding.     

Regulation of rat growth hormone gene expression in tissue culture: influence of cell growth phase

The effect of sustained stress on the plasma CRH level was studied in rats subjected to the stress of laparotomy conducted under ether anesthesia or water immersion-restraint. The role of AVP in ACTH secretion during such stress was also investigated. Concentrations of CRH and AVP in the hypothalamus, extrahypothalamic tissues and peripheral blood were measured by radioimmunoassays. Persistent secretion of ACTH was observed from 10 or 30 min to 120 min after the onset of each stress. Plasma CRH levels rose significantly 10 min after the onset of ether-laparotomy stress and remained significantly elevated at 120 min compared with controls. In the animals subjected to water immersion-restraint stress, plasma CRH tended to increase during the time course of the stress, reaching levels that were at least two times higher than the control. CRH concentrations in the median eminence (ME) during both types of stress decreased significantly at 120 min. In the ether-laparotomy stressed rats, CRH in the neurointermediate lobe (NIL) decreased significantly at 120 min, similar to the ME. Although a significant change in the adrenal CRH content was observed in the ether-laparotomy stressed rats, the involvement of adrenal CRH in ACTH secretion is unlikely as the absolute change in CRH was very small. These findings suggest that continuous CRH increase reflects a persistent secretion of CRH from the hypothalamic median eminence to the hypophysial portal vessels. It is possible that CRH secretion from the posterior pituitary gland is at least partly responsible for the persistent plasma ACTH increase in ether-laparotomy stress.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of chronic stress on memory processes in the tree shrew

Unpredictable and uncontrollable stressful events have been shown to affect cognitive processes. Interestingly, only hippocampus-mediated memory processes are thought to be sensitive to the effects of chronic stress. In contrast, the hippocampus-independent memory processes have been shown to be resistant to chronic stressful experiences. A central feature of the stress response is the activation of the hypothalamus-pituitary-adrenocortical (HPA)-axis, resulting in increased plasma levels of glucocorticoids, and several studies suggested that the performance of hippocampus-mediated memory processes might be directly modulated by these adrenal steroids. We investigated the impact of chronic psychosocial stress on hippocampus-mediated and hippocampus-independent memory processes in male tree shrews. By using a modified holeboard we followed memory performance during 23 weeks of alternating stress-free and stressful conditions. This schedule was designed to mimic a more realistic situation with stress-free conditions being sequentially interrupted by challenging events. The results indicate that chronic stress differentially affects hippocampus-mediated and hippocampus-independent memory processes in tree shrews. While hippocampus-independent memory processes remained unimpaired throughout the study, hippocampus-mediated memory was persistently impaired, not only during stress periods but also during recovery periods. This persistent impairment seems not to be exclusively triggered by glucocorticoids because urinary free cortisol concentration returned to normal during recovery periods. The present study is the first to evaluate the consequences of sequential stress exposure on memory performance in animals. Apparently, the mechanisms modulating cognitive processes are far from being understood and need a very systematic analysis in animal models with a high face and predictive validity to human stress-related memory disorders.     

Increased mRNA for corticotrophin releasing hormone in the amygdala of fawn-hooded rats: a potential animal model of anxiety

Compared to the outbred Wistar rat strain, the Fawn-hooded rat strain has several characteristics which suggest that the Fawn-hooded strain is hyperaroused. Fawn-hooded rats exhibit more freezing behavior in response to stress, have an increased preference for alcohol, develop adult onset hypertension, and have elevated urinary catecholamine levels. We used quantitative in situ hybridization to investigate central components of the corticotropin releasing hormone (CRH), arginine vasopressin (AVP) and noradrenergic stress response and arousal systems in these rats. We also measured basal corticosterone levels and adrenal weights to assess tonic hypothalamic-pituitary-adrenal axis activity. Compared to Wistar rats, Fawn-hooded rats had significantly increased CRH mRNA in the central nucleus of the amygdala and reduced CRH mRNA in the paraventricular nucleus of the hypothalamus. Fawn-hooded rats also bad reduced AVP mRNA expression in the parvocellular cells of the hypothalamic paraventricular nucleus. There were no differences between strains in glucocorticoid receptor mRNA in the hippocampus or the paraventricular nucleus or in mineralocorticoid receptor mRNA in the hippocampus. There was also no difference between strains in tyrosine hydroxylase mRNA in the locus ceruleus. Finally, adrenal weights were significantly reduced in the Fawn-hooded rats while basal corticosterone levels were similar in the two strains, which suggests central hypoactivity of the hypothalamic-pituitary-adrenal axis in Fawn-hooded rats compared to Wistar rats. Increased CRH mRNA in the central nucleus of the amygdala and reduced tonic hypothalamic-pituitary-adrenal axis activity may play a role in the unique behavioral and physiological characteristics of Fawn-hooded rats.     

Status of somatostatin receptor messenger RNAs and binding sites in rat brain during kindling epileptogenesis

In situ hybridization histochemistry with somatostatin sst1-sst5 receptor messenger RNA-selective oligoprobes and quantitative receptor autoradiographic binding studies using [125I]Tyr3-octreotide, [Leu2,D-Trp22,125I-Tyr25]somatostatin-28 and [125I]CGP 23996 ([125I]c[Asn-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) were performed to determine the level of expression of somatostatin receptor messenger RNA and receptor binding sites in the hippocampal formation, limbic system and cerebral cortex of adult rats electrically kindled in the dorsal hippocampus. In control rats (implanted with electrodes but not electrically stimulated), the somatostatin-1 receptor-selective [125I]Tyr3-octreotide and the non-subtype-selective [Leu3,D-Trp22,125I-Tyr25]somatostatin-28 preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the molecular layer of the dentate gyrus, the subiculum and presubiculum of the hippocampal formation, the inner layer of the frontal cortex, and the lateral and basolateral nuclei of the amygdala. The non-subtype-selective radioligand [125I]CGP 23996 (in 5 mM Mg2+ buffer) preferentially labelled the strata oriens and radiatum of the CA1 subfield of the hippocampus, the subiculum and the basolateral nucleus of the amygdala. Under conditions where primarily somatostatin-2 receptors were labelled, [125I]CGP 23996 (in 120 mM Na+ buffer) showed strong binding in the strata oriens and radiatum of the CA1 subfield of the hippocampus and the frontal cortex, whereas the dentate gyrus, subiculum and amygdala showed only weak signals. During and after kindling, no significant differences were observed between the ipsi- and contralateral sides of the hippocampus. A significant decrease (about 40%) of somatostatin receptor binding sites was observed in the molecular layer of the dentate gyrus with all radioligands (except [125I]CGP 23996 in Na+ buffer, which did not label this area) at stage 2 (pre-convulsive stage) and one week, but not one month, after stage 5 (generalized motor seizures). In contrast to somatostatin receptor binding, no alterations of the messenger RNA levels for sst1-sst5 receptors were found either at stage 2 or at stage 5. Similarly, no changes in receptor binding or messenger RNA levels were observed in the brain of rats which experienced a single afterdischarge. The present study shows a significant and selective decrease of somatostatin-1 receptor binding sites in the dentate gyrus of kindled rats. This is part of the plastic changes induced by kindling and may contribute to the increased sensitivity for the induction of generalized seizures during kindling.     

Functional imaging, affective disorder and dementia

Perfusion imaging has had modest success thus far in mood disorder. The most consistent findings in both primary major depression and in secondary depression have been reductions in inferior frontal cortex, adjacent cingulate cortex, temporal cortex and basal nuclei. They are compatible with a primary network for the integration of emotional experience in inferior frontal cortex, striatum and amygdala which is partially supported by the findings from relevant lesions and activation studies in normal controls. There are additional findings implicating dorso-lateral prefrontal and adjacent medial/limbic cortex in some patient groups. In elderly men particularly, reductions in prefrontal cortex appear to correlate with cognitive impairment. In dementia, perfusion imaging with single photon emission tomography (SPET) is becoming established as an important clinical tool ancillary to neuropsychological testing. Quantitation and statistical definitions of regional abnormality will be worthwhile innovations as camera systems become more technically advanced.     

Concomitant infusion of ovine corticotropin-releasing hormone does not prevent suppression of the hypothalamus-pituitary-adrenal axis by dexamethasone in male rats

Glucocorticoids (GCs) suppress the hypothalamus-pituitary-adrenal (HPA) axis at various sites including hypothalamus, pituitary and extrahypothalamic brain. Previous studies have shown that corticotropin-releasing hormone (CRH) and vasopressin facilitate the recovery of HPA axis suppressed by GCs. In this study, we investigate whether the concomitant continuous infusion of CRH may prevent the suppression of HPA axis by GCs. Groups of male Wistar rats weighing 140 to 160 g were implanted subcutaneously with Alzet osmotic pump for delivery of dexamethasone (DEX), 2 micrograms/h and/or CRH, 0.66 microgram/h. Control rats were implanted with sialistic tube of similar size. Rats were decapitated 3 or 7 days after osmotic pump implantation. In spite of the suppression of plasma corticosterone, the body weight (BW), adrenal weight (AW), plasma corticotropin (ACTH) and pituitary ACTH content of rats treated with DEX for 3 days were not significantly different from those of control rats. Concomitant infusion of ovine CRH (oCRH) and DEX for 3 days caused impaired BW gain, adrenal atrophy in addition to further reduction of plasma corticosterone. Treatment with DEX and/or oCRH for 7 days caused further suppression of HPA axis as shown by reduced pituitary ACTH content. In conclusion, simultaneous infusion of oCRH and DEX does not prevent and may even worsen HPA axis suppression by DEX.     

Solubilization and biochemical characterization of the human myometrial corticotrophin-releasing hormone receptor

We have solubilized an active form of the myometrial corticotrophin-releasing hormone (CRH) receptor using 1% w/v digitonin. The solubilized receptor retains its capacity for high-affinity binding as demonstrated by Scatchard analysis, although there was a shift in dissociation constant (Kd) from 83.6 +/- 15-195 +/- 35 pM for the membrane-bound and soluble receptor respectively. There was no difference in the maximum binding site concentrations (Bmax) of 13 +/- 5 and 21.5 +/- 6 fmol/mg protein for the membrane-bound and soluble receptor respectively. Sauvagine unlike CRH had no effect on radiolabeled CRH binding which suggests that the CRH-R2 receptor is not present in the myometrium. The solubilized receptor did not retain guanine-nucleotide sensitivity. The isoelectric focusing (IEF) profile of the human myometrial CRH receptors was significantly different from that of the rat cerebral cortex. Furthermore, solubilization of human myometrial membrane proteins followed by gel filtration and SDS-PAGE revealed a specifically labeled protein with an apparent molecular weight of 42000-47000 kDa. Our results suggest that during solubilization the human myometrial CRH receptor is dissociated from the guanine nucleotide-binding protein (Gs) and that high affinity binding for soluble CRH receptors is not dependent on the coupling of a guanine nucleotide-binding protein.     

Contextual modulation of conditioned responses: Role of the ventral subiculum and nucleus accumbens.

The performance of conditioned responses (CRs) is diminished when trained subjects are tested in a novel context. This study tested the hypothesis that the flow of contextual information along the disynaptic "ESA" (entorhinal cortex-ventral subiculum-nucleus accumbens) pathway is responsible for context-related modulation of CRs. Rabbits received electrolytic or sham lesions of the ventral subiculum followed by discriminative avoidance conditioning and counterbalanced extinction sessions in the original training context, a novel context, and the original training context with a novel cue. Neuronal activity was recorded simultaneously in the nucleus accumbens, cingulate cortex, and basolateral amygdala. The lesions did not affect the acquisition of avoidance behavior or prevent the reduction of CRs in response to a novel cue. However, the lesions did reduce CR incidence during extinction, and they did eliminate a further novel-context-induced CR reduction found in controls. In addition, lesions disrupted context-dependent neuronal responses in the nucleus accumbens but not in the cingulate cortex or amygdala. These findings are interpreted as supportive of the hypothesis that the ESA pathway mediates contextual modulation of CRs during extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural correlates of species-typical behavior in the Syrian golden hamster.

The behavior of a total of 84 Syrian golden hamsters with lesions to the medial frontal cortex (MF), orbital frontal cortex (OF), cingulate cortex (CING), posterior cortex (POST), hippocampus (HPC), septum (SEPT), or amygdala (AMYG) was compared with that of 12 control hamsters in a variety of situations, including weight regulation, food hoarding, nest building, neophobia, bait shyness, sex preference, territorial aggression, and shock-induced aggression. The behavior of Ss with OF or AMYG lesions was doubly dissociable from the behavior of Ss with MF, HPC, or SEPT lesions. The OF and AMYG lesions produced severe weight losses, and all OF Ss were aphagic and adipsic and subsequently died. The HPC, MF, and SEPT lesions severely disrupted hoarding and nest building, whereas the other lesions affected neither. None of the lesions impaired the development of bait shyness when a sucrose solution was paired with sickness, but both AMYG and SEPT lesions may have produced a mild impairment when an NaCl solution was paired with sickness. Only amygdala lesions produced consistent behavioral changes on the social tests. Neither cingulate nor posterior cortical lesions significantly altered behavior on any of the tests. Results support the idea that different forebrain regions can be functionally dissociated by using behavioral tests that are biologically significant. (56 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)