Sympathetic-adrenal medullary response to stress in hyperactive and hypertensive rats

Sympathetic-adrenal medullary hyperreactivity to acute stress, measured as an exaggerated elevation of plasma epinephrine and norepinephrine levels in response to footshock, was examined in four genetically related, inbred rat strains, all derived from the Wistar-Kyoto rat (WKY). These four strains are endowed with the traits of hypertension and behavioral hyperactivity, expressed either together (in SHR), or separately in two new strains (Wistar-Kyoto hyperactive rats, WK-HA, and Wistar-Kyoto hypertensive rats, WK-HT), or not at all (in WKY). Male rats of the SHR, WKY, WK-HA and WK-HT strains were subjected to acute footshock stress in order to determine whether the previously reported hyperreactivity of the SHR is attributable to the hypertensive trait, or to the behavioral hyperactivity trait, both of which are characteristic of the SHR. Plasma catecholamine levels were determined prior to, immediately following, and 5 min following acute footshock stress. We report here that the WK-HA strain (hyperactive but not hypertensive) exhibited the hyperreactivity characteristic of SHRs, and not the WK-HT strain (hypertensive but not hyperactive). We conclude that the exaggerated sympathetic-adrenal medullary response to acute stress is associated with the hyperactivity trait and not with hypertension among these congenic rat strains.     

Changes in heart rate and body temperature during passive avoidance behavior in rats

Heart rate, core temperature and gross locomotor activity during passive avoidance behavior in rats were recorded by a telemetry system connected to a computer data acquisition program. Passive avoidance latency and approach to the dark compartment were evaluated. Rats were assigned to five different groups, i.e., the shock groups that received different intensities of footshock (0.15, 0.25 and 1.0 mA, respectively, for 3 sec), a no footshock control group and a group that had no access to the dark compartment (i.e., no dark compartment control group). Retention tests were carried out 24 and 120 hr after the learning trial. Rats exposed to footshock showed a decrease in heart rate during the first 10 sec of the observation period in both retention tests. An average bradycardia was found in the lowest shock intensity group (0.15 mA) at both the 24- and 120-hr retention test whereas the other two groups (0.25 and 1.0 mA) showed a gradual increase in heart rate. This increase was more pronounced the longer the rats stayed on the platform. Similarly, a gradual rise in core temperature was observed in these rats as well as in the no dark compartment control group. The number of approaches to the dark compartment was significantly depressed in the group exposed to 1.0 mA footshock intensity. Gross locomotor activity was reduced in animals that exhibited maximum avoidance latency. Exposure of rats to the above-described behavioral paradigms induced autonomic activation resulting in changes in heart rate and temperature. These changes were not caused by gross locomotor activity and may thus be related to the various behavioral states.(ABSTRACT TRUNCATED AT 250 WORDS)     

Behavioral response of the genetically obese (ob/ob) mouse to heat stress: effects of naloxone and prior exposure to immobilization stress

Genetically obese (ob/ob) mice, which possess abnormally elevated levels of pituitary β-endorphin and adrenocorticotropin exhibited less grooming, rearing and jumping during a five min exposure to different levels of heat stress compared to their lean littermate controls (ob/?). Naloxone had a diametrically opposite effect on rearing in these animals, particularly when exposed to low heat stress; it enhanced rearing in ob/ob mice and suppressed the rearing response in ob/? mice. Naloxone enhanced jumping in both the ob/ob mice and the ob/? mice. This effect was slightly, although not significantly, stronger in the obese mice. Finally, exposure to 10 min of immobilization stress before testing at 46°C, enhanced grooming and suppressed jumping in ob/ob and ob/? mice. Naloxone pretreatment reversed the effect of immobilization stress in ob/ob mice but not in their lean littermate controls. The data is discussed in terms of the differential involvement of pituitary endorphins in the behavioral response of ob/ob and ob/? mice to stress.     

P-CPA pretreatment reverses the changes in sleep and behavior following acute immobilization stress rats

The effects of p-CPA (para-chlorophenylalanine) pretreatment was studied on the sleep-wake parameters and patterns of behavioral activities in an animal model of acute immobilization stress. For the experiments, young male Charles Foster rats were divided into three groups, subjected to (i) acute immobilization stress for four hours on specially designed wooden boards, (ii) a similar model of acute immobilization stress after pretreatment of p-CPA (injected through i.p. route), and (iii) control rats (p-CPA untreated and unstressed). Three channels of electrographic signals, i.e., EEG (electroencephalogram), EOG (electrooculogram), and EMG (electromyogram) were recorded continuously for four hours for all three groups of rats to analyze the changes in sleep-wake stages. The assessment of behavior was performed just after the stress on separate groups of rats in Open-Field (OF) and Elevated Plus-Maze (EPM) apparatuses. The significant changes in total sleep time (P < 0.05), total time for rapid eye movement sleep (P < 0.01), and total time in wakefulness (P < 0.01) following acute immobilization stress were found reversed in the p-CPA (a serotonin inhibitor) pretreated group of rats. Simultaneously, the results of the present work also revealed that the changes in grooming behavior (P < 0.05) in OF and the total time spent on the center of EPM (P < 0.05) were observed altered in p-CPA pretreated group of rats.     

Involvement of central angiotensin receptors in stress adaptation.

The present study examined the effects of acute and chronic neurogenic stressors on the expression of two distinct angiotensin receptors in two stress-related brain nuclei: angiotensin type 1A receptor in the paraventricular nucleus of the hypothalamus and angiotensin type 2 receptor in the nucleus locus coeruleus. Male Wistar rats were divided into four experimental groups. The first two groups were subjected once to an acute 90-min immobilization or air-jet stress session, respectively. The other two groups were subjected to 10 days of daily 90-min immobilization sessions and, on the 11th day, one group was exposed to an additional 90-min immobilization and the other to a single air-jet stress (heterotypic but still neurogenic) session. In each group, rats were perfused before stress (0 min), immediately following stress (90 min) or 150, 180, 270 or 360 min (and 24 h in chronic immobilization) after the beginning of the last stress session. Basal expression of both angiotensin receptor subtype 1A and angiotensin receptor subtype 2 messenger RNA was minimal in non-stressed animals. Acute immobilization as well as air-jet stress induced similar patterns (time-course and maximal values) of angiotensin receptor subtype 1A messenger RNA expression in the paraventricular nucleus. Angiotensin receptor subtype 1A messenger RNA expression increased 90-150 min after the beginning of the stress and returned to basal levels by 360 min. Chronic stress immobilization slightly modified the pattern, but not maximal values of angiotensin receptor subtype 1A messenger RNA expression to further immobilization (homotypic) or air-jet stress (heterotypic). Acute immobilization and air-jet stress sessions induced similar locus coeruleus-specific angiotensin receptor subtype 2 messenger RNA expression. This expression increased 90 min following the onset of the stress session and remained elevated for at least 360 min. Chronic immobilization stress increased angiotensin receptor subtype 2 messenger RNA expression to levels comparable to those observed in acute stress conditions. Novel acute exposure to neurogenic stressors did not further increase these levels in either homotypic (immobilization) or in heterotypic (air-jet stress) conditions. These results suggest that central angiotensin receptors are targets of regulation in stress; therefore, stress may modulate angiotensin function in the paraventricular nucleus and locus coeruleus during chronic exposure to neurogenic stressors.     

α-MSH levels in cerebrospinal fluid and blood of rats during behavioral manipulations

It was shown previously that α-MSH levels in peripheral blood of rats subjected to passive avoidance training did not correlate with the behavioral performance of the animals. We have investigated whether α-MSH levels in cerebrospinal fluid (CSF) change during passive avoidance behavior. It appeared that throughout adaptation, acquisition and retention of this avoidance behavior, α-MSH levels in the CSF did not change significantly. In an additional experiment in which the effects of an electric footshock versus a psychological stimulus were tested, α-MSH levels in CSF also remained unchanged. Since CSF α-MSH levels appear to be relatively stable under these behavioral conditions, it seems unlikely that the CSF functions as a direct and specific route for the afferent transport of the behaviorally active neuropeptide α-MSH to its sites of action in the brain. However, the psychological stimulus, which consisted of the fear of receiving an unavoidable electric footshock, did induce a significant enhancement of α-MSH levels in peripheral blood, suggesting that psychological stress may be involved in the release of α-MSH into the peripheral circulation. These results support the idea of a differentiated system of secretion of α-MSH into CSF and peripheral blood.     

Modulatory effects of norepinephrine in the lateral bed nucleus of the stria terminalis on behavioral and neuroendocrine responses to acute stress

The brain noradrenergic system is activated by stress, and modulates the activity of forebrain regions involved in behavioral and neuroendocrine responses to stress, such as the lateral bed nucleus of the stria terminalis (BSTL). This region of the limbic forebrain receives dense noradrenergic innervation, and has been implicated in both anxiety and regulation of the hypothalamic-pituitary-adrenal axis. We hypothesized that stress-induced release of norepinephrine in the BSTL modulates anxiety-like behavioral responses to stress and activation of the hypothalamic-pituitary-adrenal stress axis.Using microdialysis, we showed that release of norepinephrine was increased in the BSTL of male Sprague-Dawley rats during immobilization stress. In the next experiment, we then microinjected noradrenergic antagonists into the BSTL immediately prior to acute immobilization stress to examine noradrenergic modulation of behavioral stress reactivity. Either the alpha(1)-receptor antagonist benoxathian, or a cocktail of beta(1)- and beta(2)-receptor antagonists (betaxolol+ICI 118,551) blocked the anxiety-like reduction in open-arm exploration on the elevated plus-maze, but not the reduction in social behavior induced in the social interaction test. In a third experiment, benoxathian reduced plasma levels of adrenocorticotropic hormone following stress, but beta-receptor antagonists had no effect.From these results we suggest that stress-induced norepinephrine release acts on both alpha(1)- and beta-receptors in the BSTL to facilitate anxiety-like behavioral responses on the plus-maze but not the social interaction test, and modulates hypothalamic-pituitary-adrenal axis activation via alpha(1)-receptors only. Together with previous results in which adrenergic antagonists in central amygdala attenuated behavioral responses on the social interaction test but not the plus-maze, these observations suggest the two behavioral tests measure different dimensions of stress reactivity, and that norepinephrine facilitates different components of the stress response by region- and receptor-specific mechanisms.     

Differential influences of different stressors upon midbrain raphe neurons in rats

Various types of stressors were given to different groups of animals to examine their effects on the mesostriatal and mesolimbic serotonergic pathways. Results indicate that shock-induced fighting experience preferentially decreased serotonin (5-HT) levels in the dorsal raphe and striatum, while air puff stimulation selectively lowered 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) contents in the median raphe and hippocampus. Both immobilization and light footshock stress have a more consistent effect on both serotonergic systems. These results suggest that different stressors have differential influences upon central 5-HT neurons and, other than anatomical differentiation, these serotonergic neurons are not homogeneous with respect to their responses to stress either.     

Anti-stress effects of cilnidipine and nimodipine in immobilization subjected mice

The present study was designed to investigate the ameliorative role of cilnidipine and nimodipine in immobilization stress-induced behavioral alterations and memory defects in the mice. Acute stress was induced by immobilizing the mice for 150 min and stress-induced behavioral changes were assessed using actophotometer, hole board, open field and social interaction tests. The learning and memory was evaluated using elevated plus maze tests and biochemically, the corticosterone levels were measured in the blood serum. Acute immobilization stress resulted in decrease in locomotor activity, frequency of head dips and rearings in hole board; line crossing and rearing in the open field; increase in avoidance in social behavior along with development of memory deficits assessed by an increased transfer latency time and elevation of the corticosterone levels. Administration of cilnidipine (10 mg/kg), an L and N-type dual calcium channel blocker, and nimodipine (10 mg/kg), an L-type calcium channel blocker, significantly attenuated the immobilized stress-induced behavioral changes and restored memory deficits along with normalization of the corticosterone levels. Cilnidipine and nimodipine produced comparable beneficial effects in restoring immobilization stress subjected mice. It may be concluded that cilnidipine and nimodipine mediated attenuation of corticosterone release by blockage of calcium channels (both L and N-type) on the HPA-axis is responsible for beneficial effects in restoration of behavioral alterations and memory deficits in immobilization-induced acute stress in mice.     

Elective tolerance to behavioral effects of neurotensin

Neurotensin reduces locomotor activity in an open field situation as well as responsiveness to electric footshock. Repeated injections of neurotensin in combination with repeated testing of locomotor activity in the open field as well as repeated injections of neurotensin without such testing in the open field do not result in a reduction of locomotor activity. These findings make development of tolerance to this behavioral effect of neurotensin likely. Such a development of tolerance to neurotensin is not observed for the effect on responsiveness to electric footshock.     

Circadian rhythmicity and behavioral depression: I. Effects of stress

Rats were exposed to repeated sessions of inescapable footshock, and behavioral depression was subsequently assessed by measuring escape performance during exposure to escapable shock in a different testing environment. Free-running circadian activity rhythms were assessed using running wheels for approximately three weeks before and after administration of inescapable shock. Several animals showed lengthening of free-running period and decreases in activity level following shock. Similar effects were also seen in rats that were removed from their running wheels, placed within the shock apparatus, and not given shock, but not in nonhandled control animals. Furthermore, period lengthening in shocked and handled rats was positively correlated with escape performance, suggesting that circadian rhythm alterations occurred in those animals that were best able to cope with shock or handling-related stressors. In contrast, individual differences in circadian period and activity level during baseline conditions were not predictive of either escape performance or circadian rhythm alterations. These results suggest that successful behavioral adaptation to stress may be associated with alterations of circadian rhythmicity.     

Fos expression following regimens of predator stress versus footshock that differentially affect prepulse inhibition in rats

Stress is suggested to exacerbate symptoms and contribute to relapse in patients with schizophrenia and several other psychiatric disorders. A prominent feature of many of these illnesses is an impaired ability to filter information through sensorimotor gating processes. Prepulse inhibition (PPI) is a functional measure of sensorimotor gating, and known to be deficient in schizophrenia and sometimes in post-traumatic stress disorder (PTSD), both of which are also sensitive to stress-induced symptom deterioration. We previously found that a psychological stressor (exposure to a ferret without physical contact), but not footshock, disrupted PPI in rats, suggesting that intense psychological stress/trauma may uniquely model stress-induced sensorimotor gating abnormalities. In the present experiment, we sought to recreate the conditions where we found this behavioral difference, and to explore possible underlying neural substrates. Rats were exposed acutely to ferret stress, footshock, or no stress (control). 90 min later, tissue was obtained for Fos immunohistochemistry to assess neuronal activation. Several brain regions (prelimbic, infralimbic, and cingulate cortices, the paraventricular hypothalamic nucleus, the paraventricular thalamic nucleus, and the lateral periaqueductal gray) were equally activated following exposure to either stressor. Interestingly, the medial amygdala and dorsomedial periaqueductal gray had nearly twice as much Fos activation in the ferret-exposed rats as in the footshock-exposed rats, suggesting that higher activation within these structures may contribute to the unique behavioral effects induced by predator stress. These results may have implications for understanding the neural substrates that could participate in sensorimotor gating abnormalities seen in several psychiatric disorders after psychogenic stress.     

Neonatal stress in lambs: Behavioral and physiological responses

For the 1st 5 weeks after birth, experimental lambs reared in small flocks under conditions that approximated the normal social environment for sheep were subjected 3 times a week to an experimental procedure that was designed to expose the lambs to neonatal stress. The experimental procedure consisted of maternal separation, handling, and exposure to a Pavlovian conditioning paradigm. Each lamb responded to this experimental procedure with elevated plasma corticosteroid levels and intense vocalization. In contrast to the experimental (or neonatal stressed) lambs, the control lambs remained undisturbed with their mothers during the time the experimental lambs were being stressed. When both groups of lambs were subsequently exposed to open-field testing, the 2 groups did not differ in their behavioral responses (e.g., vocalization, latency to 1st movement, or locomotion) even though each of these behaviors has been found to be sensitive to the effects of neonatal social experience. Also no difference existed between the 2 groups in their initial adrenocortical response to open-field testing; however, the plasma concentration of corticosteroids of the experimental lambs took longer to return to pretest levels. At 5 months of age, the lambs were subjected to brief restraint in a dark chamber, and the effect of this brief stress on heart rate and plasma corticosteroids was measured. No differences were found between the 2 groups in either the heart rate or adrenocortical response to this stress. Thus, we have no evidence from these studies that neonatal stress had any effect on the lambs' subsequent ability to respond to brief behavioral stress.     

Changes in vasoactive intestinal peptide and arginine vasopressin expression in the suprachiasmatic nucleus of the rat brain following footshock stress

The neuropeptides, arginine vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) are synthesized by neurons of the suprachiasmatic nucleus (SCN) of the hypothalamus and are important regulators of SCN function. Previous studies have demonstrated that acute exposure to stressors can disrupt circadian activity rhythms, suggesting the possibility of stress-related alterations in the expression of these neuropeptides within SCN neurons. In this study, we examined the effect of intermittent footshock stress on AVP mRNA and heterogeneous nuclear RNA (hnRNA) and VIP mRNA expression in neurons of the SCN. Young adult male Sprague/Dawley rats were subjected to 15 s of scrambled intermittent footshock (0.50 mA pulses, 1 pulse/s, 300 ms duration) every 5 min for 30 min. Animals were sacrificed 75 or 135 min after the onset of stress and brains examined for AVP mRNA and hnRNA, and VIP mRNA using in situ hybridization. Footshock stress increased AVP hnRNA levels at the 75 min time point whereas AVP mRNA was elevated at both the 75 and 135 min time points. In contrast, footshock stress decreased the number of cells expressing VIP mRNA in the SCN without changing hybridization level per cell. These data indicate that the disruptive effect of stress on activity rhythms correlate with alterations in the expression of regulatory peptides within the SCN.     

Acetylcholine release in the hippocampus during the operant conditioned reflex and the footshock stimulus in rats

The activity of the septo-hippocampal cholinergic pathway was investigated by measuring changes in the extracellular acetylcholine (ACh) levels in the hippocampus, by means of microdialysis, during the operant conditioned reflex and the repeated footshock stimulus. Microdialysis samplings were conducted in a Skinner box where lights were delivered as conditioned stimuli (CS) paired with footshocks as unconditioned stimuli (US). Two groups of rats were used. Extracellular ACh and choline (Ch) in samples collected at 6min intervals were assessed by high-performance liquid chromatography with electrochemical detection. The elevation of hippocampus ACh was observed in the two experimental groups. The increase in ACh during aversive stimulus (footshock) was significantly larger and was probably related to the number of footshocks. There might be moderate increase in the hippocampal ACh release during the retrieval of information. The concentration of choline showed no significant fluctuation in the two groups during the whole process. This experiment explored in more detail hippocampal cholinergic activity in relation to the two different procedures.     

Lymphoid structure of the spleen in rats exposed to acute emotional stress

The objects of this investigation were the sections of the spleen and peripheral blood smears of 40 male Wistar rats of control and experimental groups that were stained using histological and histochemical methods. The rats of experimental groups were killed by decapitation immediately after discontinuation of an emotional stress (exposure to a combination of immobilization and electric skin stimulation for one hour). The changes of cellular composition and cytoarchitectonics of different functional zones of the spleen were estimated. It was found that following the emotional stress the number of small lymphocytes in the periarterial lymphoid sheath (PALS) decreased as compared to that one in control groups. At the same time, the amount of cells in PALS with the signs of destruction increased (from single cells in the animals of control groups to 7.7 and 1.5% in rats of the experimental groups that were predisposed or resistant to stress, respectively). The proportion of T-lymphocytes per PALS unit area in the spleen of experimental rats, predisposed or resistant to stress, decreased 1.6 and 1.2 times, respectively, in comparison to the control groups.     

Stress-induced enhancement of fear conditioning and sensitization facilitates extinction-resistant and habituation-resistant fear behaviors in a novel animal model of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is characterized by stress-induced symptoms including exaggerated fear memories, hypervigilance and hyperarousal. However, we are unaware of an animal model that investigates these hallmarks of PTSD especially in relation to fear extinction and habituation. Therefore, to develop a valid animal model of PTSD, we exposed rats to different intensities of footshock stress to determine their effects on either auditory predator odor fear extinction or habituation of fear sensitization. In Experiment 1, rats were exposed to acute footshock stress (no shock control, 0.4 mA, or 0.8 mA) immediately prior to auditory fear conditioning training involving the pairing of auditory clicks with a cloth containing cat odor. When presented to the conditioned auditory clicks in the next 5 days of extinction testing conducted in a runway apparatus with a hide box, rats in the two shock groups engaged in higher levels of freezing and head out vigilance-like behavior from the hide box than the no shock control group. This increase in fear behavior during extinction testing was likely due to auditory activation of the conditioned fear state because Experiment 2 demonstrated that conditioned fear behavior was not broadly increased in the absence of the conditioned auditory stimulus. Experiment 3 was then conducted to determine whether acute exposure to stress induces a habituation resistant sensitized fear state. We found that rats exposed to 0.8 mA footshock stress and subsequently tested for 5 days in the runway hide box apparatus with presentations of nonassociative auditory clicks exhibited high initial levels of freezing, followed by head out behavior and culminating in the occurrence of locomotor hyperactivity. In addition, Experiment 4 indicated that without delivery of nonassociative auditory clicks, 0.8 mA footshock stressed rats did not exhibit robust increases in sensitized freezing and locomotor hyperactivity, albeit head out vigilance-like behavior continued to be observed. In summary, our animal model provides novel information on the effects of different intensities of footshock stress, auditory-predator odor fear conditioning, and their interactions on facilitating either extinction-resistant or habituation-resistant fear-related behavior. These results lay the foundation for exciting new investigations of the hallmarks of PTSD that include the stress-induced formation and persistence of traumatic memories and sensitized fear.     

Suppression of stress immobilization-induced phosphorylation of ERK 1/2 by biting in the rat hypothalamic paraventricular nucleus

We have previously reported that acute immobilization stress induces Fos protein. Fos protein is generally used as a marker for neuronal activity and has been linked to phosphorylation of extracellular signal-regulated protein kinase 1/2 (pERK1/2), in the hypothalamic paraventricular nucleus (PVN). Biting behavior during the period of stress reduced the expression of Fos protein. The present immunohistochemical study was designed to determine whether acute immobilization stress induces pERK1/2 in the PVN, and whether the stress-induced pERK1/2 was attenuated by simultaneous biting behavior. Acute immobilization stress, in increments of up to 15min, produced detectable amounts of pERK1/2 that were proportional to the interval of stress. Biting during the acute immobilization stress significantly reduced the amount of detectable pERK1/2. These results suggest that biting activity during acute stress inhibits pERK1/2 in this region of the brain. It is feasible that the neuronal cellular response to acute stress is regulated, in some part, by inhibition of pERK1/2 by biting.     

Effects of prenatal stress on stress-induced changes in behavior and macrophage activity of mice

The present study analyzed the effects of maternal stress on behavior and macrophage activity of mice. Pregnant mice received a daily footshock (0.2 mA) from gestational days 15 (GD15) to 19. Experiments were performed on male offspring, challenged or not with another footshock (0.2 mA) on postnatal day 30 (PND30) or 60. The following results were obtained for maternal stress: (1) increment in locomotor activity of juvenile but not of adult mice observed in both open-field and plus-maze; (2) increment in rearing frequency of juvenile but not of adult mice observed in the open-field; (3) decrement in macrophage spreading of adult but not of juvenile mice; (4) abolishment of postnatal footshock effects in both macrophage spreading on PND30 and macrophage nitric oxide (NO) production on PND60; (5) reversion of postnatal footshock effects on H(2)O(2) spontaneous and PMA-induced release by macrophage on PND30; (6) modification of postnatal stress effects on macrophage phagocytosis on PND60. These changes were unrelated to differences in gestational parameters and did not reflect altered maternal-pup interactions or nutritional factors. The observed data provide experimental evidence that maternal stress alters behavior, and macrophage activity at the same time and in the same litter. These data were discussed in the light of possible neuroimmune interactions that involve catecholaminergic pathways.     

Endogenous α-melanotropin and central dopamine systems in physical and psychological stress

Summary The response of central dopamine (DA) systems to physical stress (10 s footshock, 0.5 mA, to naive rats) or psychological stress (10 s stay in experimental chamber 1 day after footshock) was studied in male rats in view of possible interactions between these neuron groups and endogenous -MSH. Three hours before stress, part of the animals were injected i.v. or intraventricularly with antiserum against -MSH or with inactivated normal rabbit serum (NRS).Characteristic response patterns were observed in different DA neuron groups by histochemical microfluorimetry: In substantia nigra, increased fluorescence intensity of DA neurons indicating increased neuronal activity, was seen on the first day (1) 5 min after physical stress or (2) 30 min after a first transfer to the experimental chamber without footshock, and on the second day (3) immediately after the psychological stress in rats given a footshock on the previous day, or (4) 5 min after the second stay in the experimental chamber in animals previously exposed to the chamber without shock. Hence, the reaction appears to occur faster the second day. No significant intensity changes were detected in the ventromedial tegmental DA neurons (A10). The arcuate DA neurons which i.a. control -MSH secretion, responded to physical stress or control manipulations in a complex way, while no significant reaction was seen after psychological stress. Differences between physical and psychological stress were also seen in serum levels of -MSH (determined by RIA).Intravenous antiserum against -MSH enhanced the response of nigral DA neurons to physical stress and led to elevated intensity levels 5 min after psychological stress when values were again decreasing in uninjected rats. Moreover, a marked rise in intensity was elicited after psychological stress in the A10 DA neurons where no change was detected in the absence of antiserum. Anti--MSH also affected the arcuate DA neurons in psychological stress. Intraventricular antiserum did not display any specific effects.These data point to a modulatory influence of circulating -MSH on the functional state of central DA systems. They further reveal different temporal response patterns of nigral and also arcuate DA neurons in relation to the two stress situations and to other types of manipulations considered to be less stressful.The investigation was supported by grants from the Swiss National Science Foundation (3.231-0.77 and 3.547-0.79), the Hartmann-Müller Stiftung and the Jubiläumsspende of the University of Zürich