Biomedical subjects

G B Makara

Publications and source records attributed to G B Makara.

At least 19 recordsLinked to original sources

PubMed2003

Maternal genotype influences stress reactivity of vasopressin-deficient brattleboro rats.

The role of vasopressin, cosecreted with corticotropin-releasing hormone (CRH), in stress is debated, because both normal as well as reduced adrenocorticotropin hormone (ACTH) rise to an acute challenge has been reported in Brattleboro rats genetically lacking vasopressin (di/di). Because di/di pups could be born either from di/+ (heterozygous) or from di/di mothers, and maternal influence is known to modify adult responsiveness, we investigated whether the influence of maternal genotype could explain the variability. Adult rats from mothers with different genotypes were stressed with 60 min restraint and trunk blood was collected for measuring hormone content by radioimmunoassay at the end of stress. All offspring of di/+ mothers had similar ACTH responses to restraint, while the di/di rats born to, and raised by di/di mothers showed reduced ACTH reactivity to restraint. The di/di rats showed elevated water turnover and required a daily cage cleaning every day, which meant frequent handling. To offset the role of handling, all rats had daily cage cleaning in the next series, but the results were the same as in the first series. To investigate whether lactation, the behaviour of the mother or some other factor during the pregnancy is responsible for the differences, pups from di/+ dams were raised by di/di foster mothers and vice versa. We found that the genotype of parental mother is more important than that of the foster mother. The corticosterone and prolactin elevation normally seen after acute stress was unchanged by family history, maternal or personal genotype. Furthermore, in studies with mutant animals, the rearing conditions should be controlled by the experimenter. In experiments with Brattleboro rats, the use of homozygous and heterozygous rats from the same litters of di/+ dams and di/di males is recommended. Our results suggest that vasopressin is not indispensable for ACTH release, and that the di/di genotype of the parental mother can decrease the stress reactivity of the di/di Brattleboro rats.

Acute Disease↗

PubMed2003

Role of hypothalamic inputs in maintaining pituitary-adrenal responsiveness in repeated restraint.

The role of hypothalamic structures in the regulation of chronic stress responses was studied by lesioning the mediobasal hypothalamus or the paraventricular nucleus of hypothalamus (PVH). Rats were acutely (60 min) and/or repeatedly (for 7 days) restrained. In controls, a single restraint elevated the plasma adrenocorticotropin (ACTH), corticosterone, and prolactin levels. Repeated restraint produced all signs of chronic stress, including decreased body and thymus weights, increased adrenal weight, basal corticosterone levels, and proopiomelanocortin (POMC) mRNA expression in the anterior pituitary. Some adaptation to repeated restraint of the ACTH response, but not of other hormonal responses, was seen. Lesioning of the mediobasal hypothalamus abolished the hormonal response and POMC mRNA activation to acute and/or repeated restraint, suggesting that the hypothalamo-pituitary-adrenal axis activation during repeated restraint is centrally driven. PVH lesion inhibited the ACTH and corticosterone rise to the first restraint by approximately 50%. In repeatedly restrained rats with PVH lesion, the ACTH response to the last restraint was reduced almost to basal control levels, and the elevation of POMC mRNA level was prevented. PVH seems to be important for the repeated restraint-induced ACTH and POMC mRNA stimulation, but it appears to partially mediate other restraint-induced hormonal changes.

Adrenal Glands↗

PubMed2001

The effect of glucocorticoids on the anxiolytic efficacy of buspirone.

RATIONALE: The serotonergic system and the hypothalamus-hypophysis-adrenocortical axis reciprocally influence each other. Therefore, the interaction between stress and serotonergic anxiolytics should be of major concern for both laboratory investigations and clinical treatment. OBJECTIVES: We have studied the effects of the serotonergic anxiolytic buspirone in rats in which basal levels of glucocorticoids were low and stable, while acute stress reactions were inhibited or exogenously induced. METHODS: Rats were adrenalectomised. Subcutaneous corticosterone pellets maintained basal glucocorticoid concentrations while acute changes were mimicked by corticosterone injections. Anxiety was assessed by the social interaction test. Temporal changes were evaluated by submitting rats to the same manipulations three times at two-day intervals. RESULTS: Buspirone applied to animals with stable and low plasma glucocorticoid concentrations induced a dramatic increase in social interactions. A slight locomotor suppressive effect was also noticed. The effects of buspirone proved to be stable over time in these animals. Acute treatment with corticosterone doubled the locomotor suppressive effects of buspirone and reversed its anxiolytic effects: the buspirone-corticosterone combination was anxiogenic after the first application. During the second and third treatment, the impact of corticosterone on buspirone efficacy gradually decreased, but the combined treatment remained about half as effective in reducing anxiety as buspirone alone.

Adrenalectomy↗

PubMed2001

Non-genomic effects of glucocorticoids in the neural system. Evidence, mechanisms and implications.

Complementing the classical concept of genomic steroid actions, here we (i) review evidence showing that important neural effects of glucocorticoids are exerted by non-genomic mechanisms; (ii) describe known mechanisms that may underlie such effects; (iii) summarize the functions and implications of non-genomic mechanisms and (iv) outline future directions of research. The role of non-genomic mechanisms is to shape the response of the organism to challenges that require a substantial reorganization of neural and somatic functions and involve massive behavioral shifts. Non-genomic effects may (i) prepare the cell for subsequent glucocorticoid-induced genomic changes, (ii) bridge the gap between the early need of change and the delay in the expression of genomic effects and (iii) may induce specific changes that in some instances are opposite to those induced by genomic mechanisms. The latter can be explained by the fact that challenging situations require different responses in early (acute) and later (chronic) phases. Data show that non-genomic mechanisms of glucocorticoid action play a role in both pathological phenomena and the expression of ameliorative pharmacological effects. Non-genomic mechanisms that underlie many glucocorticoid-induced neural changes constitute a for long overlooked controlling factor. Despite the multitude and the variety of accumulated data, important questions remain to be answered.

Animals↗

PubMed2001

Vasopressin pressor receptor-mediated activation of HPA axis by acute ethanol stress in rats.

The plasma arginine vasopressin (AVP), ACTH, and corticosterone levels and the hypothalamic corticotropin-releasing hormone (CRH) content were measured after oral administration of 1 ml of 75% ethanol to rats, a model known to induce acute gastric erosions and stress. Elevated plasma AVP, ACTH, and corticosterone levels were detected 1 h after ethanol administration. Treatment with the vasopressin pressor (V(1)) receptor antagonist [d(CH(2))(5)Tyr(Me)-AVP] before ethanol administration significantly reduced the ACTH and corticosterone level increases. A higher hypothalamic CRH content was measured at 30 or 60 min after ethanol administration. V(1) receptor antagonist injection, 5 min before ethanol administration, inhibited the rise in hypothalamic CRH content. The protein synthesis blocker cycloheximide prevented the hypothalamic CRH content elevation after stress. The AVP-, CRH-, and AVP + CRH-induced in vitro ACTH release in normal anterior pituitary tissue cultures was also prevented by pretreatment with the V(1) receptor antagonist. The results support the hypothesis that stress-induced AVP may not only act directly on the ACTH producing anterior pituitary cells but also indirectly at the hypothalamic level via the synthesis and release of CRH.

Adrenocorticotropic Hormone↗

PubMed2000

Ultradian corticosterone rhythm and the propensity to behave aggressively in male rats.

Ultradian fluctuations in plasma glucocorticoids have been demonstrated in a variety of species including humans. The significance of such rhythms is poorly known, although disorganized ultradian glucocorticoid rhythms have been associated with behavioural disorders. Here we report that ultradian glucocorticoid rhythms may establish the propensity to behave aggressively in male rats. Male rats were significantly more aggressive in the increasing phase of their corticosterone fluctuation when confronting a male intruder than counterparts in the decreasing phase of their corticosterone fluctuations facing such opponents. Corticosterone fluctuations were mimicked by a combination of treatments with the corticosterone synthesis inhibitor metyrapone and corticosterone. Again, males with increased plasma corticosterone levels were more aggressive than counterparts with a decreased plasma corticosterone concentration. These data suggest that the behavioural response to an aggressive challenge may vary in the same animal across the day due to the pulsating nature of corticosterone secretion. Aggressive behaviour is also episodic in humans; moreover, intermittent explosive behaviour is recognized as a psychological disorder. It can be hypothesized that a temporal coincidence between the occurrence of a challenge and a surge in plasma corticosterone concentration may be one of the factors that promote episodic aggressive outbursts.

Activity Cycles↗

PubMed2000

Housing conditions and the anxiolytic efficacy of buspirone: the relationship between main and side effects.

Serotonergic anxiolytics yield contradictory results both in the laboratory and clinically. In an attempt to investigate the cause of discrepancies, the anxiolytic effect of buspirone (0, 3 or 10 mg/kg, single treatment) was tested 1 h and 4 h after injection in rats in different housing conditions. At 1 h after drug administration, buspirone increased corticosterone production and decreased locomotor behaviour in both the elevated plus-maze and the social interaction tests. No anxiolytic-like effect was produced in either test. At 4 h after drug injection, no corticosterone or locomotor effects of buspirone were observed. In contrast, anxiolytic effects emerged in this phase. Open arm exploration and social investigation were increased in the plus-maze and social interaction test, respectively. In the plus-maze, the anxiolytic effect was significant in isolated animals only. In the social interaction test, the anxiolytic effect was stronger in isolated than in group-housed animals. When corticosterone secretion was inhibited by adrenalectomy, a full anxiolytic effect of buspirone was observed 1 h after drug administration. It appears that the side effects of buspirone have a shorter duration than the main anxiolytic effect. The buspirone-induced increase in corticosterone may have abolished the anxiolytic effects of the drug shortly after injection. Individual housing enhanced the anxiolytic efficacy of buspirone 4 h after administration.

Animals↗

PubMed2000

Radiodetoxified lipopolysaccharide fails to activate the hypophyseal- pituitary-adrenal axis in the rat.

Lipopolysaccharide (LPS) is known to raise the concentration of the circulating stress hormones such as ACTH, corticosterone and beta-endorphin. This effect of endotoxin is mediated by different immune system-released hormone-like factors (e.g. interleukins, tumor necrosis factor etc.). Gamma-ray irradiation of LPS alters its biological properties and results in a radiodetoxified LPS preparation with numerous beneficial effects and decreased toxicity. In this study we compared the neuroendocrine effects of a commercial LPS and our native and radiodetoxified LPS preparations in rats. Plasma ACTH, corticosterone and beta-endorphin levels were measured by specific radioimmunoassays 120 min after intraperitoneal LPS administration. Control animals were injected with saline. Results show a dramatic increase in all hormones after administration of commercial and our native LPS preparation. Hormone levels in saline-injected controls and radiodetoxified LPS-treated rats did not rise significantly. These results suggest that radio-detoxification disintegrated that part of the LPS molecule complex which is responsible for toxicity including an enhanced production of cytokines, which trigger the hypothalamo-pituitary-adrenal axis.

Adrenocorticotropic Hormone↗

PubMed1999

Effect of cholinergic drugs on the concentration of intracellular free calcium of rat pituitary intermediate lobe cells.

We tested the effect of cholinergic drugs on the concentration of intracellular free calcium in rat melanotropes. Acetylcholine, muscarine, carbachol, and nicotine resulted in a significant rise in this parameter. Effect of acetylcholine was reduced by atropine (non-selective muscarinic antagonist), pirenzepine (M1 muscarinic antagonist), and 4-DAMP (M3 > M1 muscarinic antagonist), but exposure to the M1 muscarinic agonist McN-A 343 resulted in a significantly smaller calcium-response than that seen in response to acetylcholine or to muscarine. This suggests the involvement of both M1 and M3 muscarinic receptors in the acetylcholine-induced calcium-rise. On the other hand, in the presence of atropine the acetylcholine-induced calcium-rise was not eliminated: this fact indicates that nicotinic receptors are also involved in the acetylcholine-induced intracellular calcium-rise. The acetylcholine-, and nicotine-induced calcium-rise was significantly reduced in presence of the neuronal-type nicotinic antagonist, mecamylamine. This suggests the involvement of a neuronal-type nicotinic receptor in the acetylcholine-induced intracellular calcium-response. Moreover, because in a further experiment almost 80% of the cells investigated responded to muscarine as well as nicotine, we conclude that both functionally active muscarinic and nicotinic receptors are present on the same cell.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1999

Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats.

Social stress models appear useful in elucidating the interrelationship between stress, mood disorders, and drug efficacy. However, reliable social stress models for females are virtually lacking. The aim of this study was to determine stress-related consequences of (a) defeat in aggressive encounters and (b) social instability, in male and female rats. Defeat in male and female subjects was induced by aggressive male residents and female residents made aggressive by surgery (mediobasal hypothalamic lesion [MBHL]), respectively. Aggressiveness of resident males and resident MBHL females was remarkably similar. Alternating isolation and mixed-sex crowding phases with membership rotation were used to induce social instability. Aggression was kept low in the latter paradigm by manipulating crowding group composition. Defeat stress reduced weight gain, and increased both adrenals and plasma corticosterone in males. Only adrenal weight was affected in females. Social instability reduced weight gain, and induced thymus involution, adrenal hypertrophy and elevated plasma corticosterone levels in females. Only weight gain and thymus weights were affected in males. It is concluded that defeat stresses males more than females, while social instability is more stressful for females than for males, if aggressive contacts are low. It is suggested that the social instability model is a good model of social stress in females.

Aggression↗

PubMed1999

Muscarinic M1 and M3 receptors are present and increase intracellular calcium in adult rat anterior pituitary gland.

Physiological and biochemical evidence indicates the existence of functional muscarinic cholinergic receptors in the anterior pituitary. The selectivity of these receptors has been characterised by studying the binding of [3H]quinuclidinyl benzilate ([3H]QNB) and [3H]diphenyl-acetoxy-N-methyl-piperidine ([3H]4-DAMP) in membrane preparation of male rat anterior pituitary at 25 degrees C. Competition experiments with receptor selective muscarinic antagonists were used to characterise specific selective muscarinic receptor binding. Both [3H]QNB and [3H]4-DAMP bound to anterior pituitary membranes at low concentrations, binding was saturable and was potently displaced by 4-DAMP (M1, M3 subtypes selective antagonist) > atropine (general) > pirenzepine (M1). Methoctramine (M2) didn't antagonise the [3H]QNB binding efficiently. Acetylcholine and carbachol increased the intracellular Ca2+ level in 62% and 65% of cultured rat anterior pituitary cells in a dose-dependent manner, and this effect was prevented by pirenzepine. Based on these results we suggest that both M1 and M3 muscarinic receptors are present and active in the majority of cells in the rat anterior pituitary gland, but their physiological role in the adult rat remains to be examined.

Acetylcholine↗

PubMed1999

Alpha 2-adrenoreceptor subtypes regulate ACTH and beta-endorphin secretions during stress in the rat.

The effect of different alpha 2-adrenoreceptor subtype agonists and antagonists on adrenocorticotrop hormone (ACTH) and beta-endorphin release induced by ether stress was examined. Ether inhalation-induced ACTH and beta-endorphin increase was inhibited by i.c.v. administration of 30 micrograms but not 1 and 10 micrograms clonidine (alpha 2-adrenoreceptor agonist). I.c.v. oxymetazoline (alpha 2A-adrenoreceptor agonist; 1-10-30 micrograms) or the alpha 1-agonist methoxamine (100 micrograms/rat) failed to inhibit the stress-induced rise. Pretreatment with the alpha 1/alpha 2B.C-antagonist prazosin (0.5 mg/kg, i.p.) prevented the effect of clonidine on the ether stress, while the alpha 1/alpha 2A-antagonist WB-4101 (0.5 mg/kg, i.p.) was unable to counteract the inhibitory effect of clonidine. Prazosin alone had no effect on the ether-induced plasma ACTH and beta-endorphin elevation. These results suggest that noradrenaline in the central nervous system may inhibit the stress-induced hypothalamo-pituitary-axis and pituitary beta-endorphin activation via alpha 2B.C-adrenoceptor subtypes and prazosin may antagonize its effect on these receptors.

Adrenergic alpha-Agonists↗

PubMed1999

Social stress of variable intensity: physiological and behavioral consequences.

Stress effects in humans depend on stress type, intensity, and duration. Animal models of social stress serve as good ways to mimic stress experienced in humans. However, the available stress paradigms pay little attention to the relationship between the intensity and the type of social stressors. The aim of the present work is to study behavioral and endocrinological consequences of social stress by varying the intensity and type of agonistic social contacts. Subjects were exposed to the attacks of an experienced fighter resident rat once a day for 4 consecutive days. Mild versus strong effects were studied by varying the length of daily confrontations (30 min vs. 4 h). The type of social confrontations was varied by ceasing or maintaining sensory contacts among contestants between encounters. Endocrinological variables were measured on the 5th day. Anxiety was assessed by means of the elevated plus-maze. The stress state depended on the length of daily encounters: 30-min encounters did not, whereas 4-h encounters did result in weight loss and chronic elevation of plasma corticosterone. The type of contacts between subjects and dominants also affected the resulting stress state: adrenal hypertrophy was obtained only when contacts between contestants were maintained between encounters. Although the mildest stress procedure (30-min encounters on 4 consecutive days) did not affect endocrinological variables, it resulted in subtle behavioral modifications that changed the anxiety-related effects of additional acute stressors. Thus, anxiety-related behavioral changes resulting from repeated mild stressors may be hidden factors that can have long-term consequences on the development of anxiety-like behavioral deficits. Results outline the necessity of studying the effects of social stressors of different intensities and different types.

Adrenal Glands↗

PubMed1999

Simultaneous blockade of two glutamate receptor subtypes (NMDA and AMPA) results in stressor-specific inhibition of prolactin and corticotropin release.

Many neurons express simultaneously two or more isotypes of glutamate receptors, so that pharmacological modulation of more than one receptor may be necessary to reveal the role of glutamate in mediating physiological processes. The present studies were aimed at evaluating involvement of endogenous glutamate in triggering plasma prolactin (PRL) and adrenocorticotropic hormone (ACTH) levels in response to three different stress stimuli (footshock, immobilization and ether stress). Blockade of glutamate receptor subtypes was achieved by the administration of the NMDA antagonist dizocilpine (MK-801, 0.2 mg/kg) and the selective AMPA antagonist GYKI 52466 (10 mg/kg). Rats were pretreated for 4-5 days and then exposed to stressful stimulation. Basal hormone levels were not affected by the antagonists. In male rats, combined, but not separate blockade of NMDA and AMPA/kainate subtypes of glutamate receptors prevented the rise in plasma PRL in response to footshock stress. In female rats, footshock-induced PRL release was inhibited even by separate blockade of NMDA receptors by dizocilpine, suggesting that the PRL system of females is more sensitive to the effect of NMDA antagonists than that of males. None of the treatments affected PRL release during immobilization or ether stress. Simultaneous blockade of NMDA and AMPA receptor subtypes resulted in a mild inhibition of immobilization-induced ACTH release without any effect on ACTH response to footshock or ether stress. The data suggest that involvement of glutamatergic pathways in neuroendocrine response during stress is selective for discrete stress stimuli and stress hormones. In addition a concerted action of glutamate on both NMDA and non-NMDA receptor subtypes is involved in the control of PRL release during footshock stress.

Adrenocorticotropic Hormone↗

PubMed1999

Local regulation of vasopressin and oxytocin secretion by extracellular ATP in the isolated posterior lobe of the rat hypophysis.

It is now widely accepted that ATP functions as a signalling substance in the nervous system. The presence of P2 receptors mediating the action of extracellular ATP in brain regions involved in hormonal regulation raises the possibility that a similar role for ATP might also exist in the neuroendocrine system. In this study, the release from the rat isolated neurohypophysis preparation of endogenous ATP, oxytocin and vasopressin (AVP) were measured simultaneously using luciferin-luciferase and RIA techniques. After 70 min preperfusion, electrical field stimulation caused a rapid increase in the amount of ATP in the effluent and the release of AVP and oxytocin also increased stimulation-dependently. Inhibition of voltage-dependent Na+ channels by tetrodotoxin (1 microM) reduced the stimulation-evoked release of AVP and oxytocin; however, the evoked release of ATP remained unaffected. The effect of endogenous ATP on the hormone secretion was tested by suramin (300 microM), the P2 receptor antagonist. Suramin significantly increased the release of AVP, and the release of oxytocin was also enhanced. ATP, when applied to the superfusing medium, decreased the release of AVP, but not that of oxytocin, and its effect was prevented by suramin. ATP (60 nmol), added to the tissues, was readily decomposed to ADP, AMP and adenosine measured by HPLC combined with ultraviolet light detection, and the kinetic parameters of the enzymes responsible for inactivation of ATP (ectoATPase and ecto5'-nucleotidase) were also determined (Km=264+/-2.7 and 334+/-165 microM and vmax=6.7+/-1.1 and 2.54+/-0.24 nmol/min per preparation (n=3) for ectoATPase and ecto5'-nucleotidase respectively). Taken together, our data demonstrate the stimulation-dependent release, P2 receptor-mediated action and extracellular metabolism of endogenous ATP in the posterior lobe of the hypophysis and indicate its role, as a paracrine regulator, in the local control of hormone secretion.

Adenosine Triphosphate↗

PubMed1998

Monosodium glutamate lesions inhibit the N-methyl-D-aspartate-induced growth hormone but not prolactin release in rats.

Large doses of glutamate administered to newborn rats damage permanently the neurones in the hypothalamic arcuate nucleus containing the growth hormone releasing hormone and the prolactin inhibiting dopamine neuron cell bodies. Since adult animals that underwent neonatal glutamate treatment still have a relatively well functioning growth hormone and prolactin system, we tested whether in the adults the excitatory amino acid sensibility is changed. After i.v. injection of different doses (10 or 30 mg/kg) of N-methyl-D-aspartate (excitatory amino acid receptor subtype agonist) growth hormone levels were significantly increased in the control groups but there was no rise in neonatally glutamate treated male and female rats. The level of prolactin was increased by N-methyl-D-aspartate, too, but the glutamate treatment had no effect on the rise. Our study suggests that systemic administration of N-methyl-D-aspartate increases plasma growth hormone level by activating the growth hormone releasing cells in the arcuate nucleus, but the intact tuberoinfundibular dopaminergic pathway is not essential for its prolactin stimulatory effect.

Animals↗

PubMed1998

Catecholaminergic involvement in the control of aggression: hormones, the peripheral sympathetic, and central noradrenergic systems.

Noradrenaline is involved in many different functions, which all are known to affect behaviour profoundly. In the present review we argue that noradrenaline affects aggression on three different levels: the hormonal level, the sympathetic autonomous nervous system, and the central nervous system (CNS), in different, but functionally synergistic ways. Part of these effects may arise in indirect ways that are by no means specific to aggressive behaviour, however, they are functionally relevant to it. Other effects may affect brain mechanisms specifically involved in aggression. Hormonal catecholamines (adrenaline and noradrenaline) appear to be involved in metabolic preparations for the prospective fight; the sympathetic system ensures appropriate cardiovascular reaction, while the CNS noradrenergic system prepares the animal for the prospective fight. Indirect CNS effects include: the shift of attention towards socially relevant stimuli; the enhancement of olfaction (a major source of information in rodents); the decrease in pain sensitivity; and the enhancement of memory (an aggressive encounter is very relevant for the future of the animal). Concerning more aggression-specific effects one may notice that a slight activation of the central noradrenergic system stimulates aggression, while a strong activation decreases fight readiness. This biphasic effect may allow the animal to engage or to avoid the conflict, depending on the strength of social challenge. A hypothesis is presented regarding the relevance of different adrenoceptors in controlling aggression. It appears that neurons bearing postsynaptic alpha2-adrenoceptors are responsible for the start and maintenance of aggression, while a situation-dependent fine-tuning is realised through neurons equipped with beta-adrenoceptors. The latter phenomenon may be dependent on a noradrenaline-induced corticosterone secretion. It appears that by activating very different mechanisms the systems working with adrenaline and/or noradrenaline prepare the animal in a very complex way to answer the demands imposed by, and to endure the effects caused by, fights. It is a challenge for future research to elucidate how precisely these mechanisms interact to contribute to functionally relevant and adaptive aggressive behaviour.

Aggression↗

PubMed1998

Acute effects of glucocorticoids: behavioral and pharmacological perspectives.

There has been evidence since the early eighties that glucocorticoids, apart from their well known chronic effects, may have acute, short-term effects. However, a lack of understanding of the molecular mechanisms of action has hampered appreciation of these observations. Mounting evidence over the years has continued to confirm the early observations on a fast corticosterone control of acute behavioral responses. We summarize experimental data obtained mainly in rats but also in other species which show: (1) that glucocorticoid production is sufficiently quick to affect ongoing behavior; (2) that there exist molecular mechanisms that could conceivably explain the fast neuronal effects of glucocorticoids (although these are still insufficiently understood); (3) that glucocorticoids are able to stimulate a wide variety of behaviors within minutes; and (4) that acute glucocorticoid production (at least in the case of aggressive behavior) is linked to the achievement of the behavioral goal (winning). The achievement of the behavioral goal reduces glucocorticoid production. It is argued that glucocorticoids are regulatory factors having a well-defined behavioral role. Both the acute (stimulatory) effects and the chronic (inhibitory) effects are adaptive in nature. The acute control of behavior by corticosterone is a rather unknown process that deserves further investigation. The pharmacologic importance of the acute glucocorticoid response is that it may readily affect the action of pharmacologic agents. An interaction between acute glucocorticoid increases and noradrenergic treatments has been shown in the case of offensive and defensive agonistic behavior. Non-behavioral data demonstrate that acute increases in glucocorticoids may interfere with other neurotransmitter systems (e.g., with the 5HT system) as well. These observations show the importance of taking into account endocrine background and endocrine responsiveness in behavior pharmacological experiments.

Animals↗