Inhibition of the pituitary-adrenal response to stress during deprivation-induced feeding.

Plasma corticosterone and plasma and pituitary ACTH concentrations were determined during feeding and after application of an acute stress at various times after food and water presentation to male rats maintained on a restricted feeding and watering schedule. Both plasma corticosterone and ACTH concentrations fell after the presentation of food and water, and this fall was accompanied by increased levels of ACTH in the pituitary gland. In addition, a rise in plasma levels of ACTH was inhibited in response to an acute stress applied at 0--5 min after presentation of food and water, but ACTH synthesis was not. This inhibition of ACTH and corticosterone secretion in response to stress was transient and dissipated as a relatively linear function of the interval between food presentation and application of the stress. The results suggest that this feeding-induced, corticosteroid-independent inhibition of pituitary-adrenal activity involves active inhibitory mechanisms operating initially on ACTH secretory processes of the pituitary and later on the synthesis of ACTH or on the secretion of hypothalamic corticotropin-releasing factor.

The deafferentation syndrome in genetically blind rats: a model of the painful phantom limb.

The hypothesis was tested which states that the somatic deafferentation syndrome is a visually prompted response to sensorimotor loss. The dorsal roots, C5-T2, were bilaterally cut in a strain of rats known to be genetically blind. These complete dorsal rhizotomies left the forelimbs totally anesthetic, analgesic and paretic. Contact and visual placing reactions were absent, and responses to pinprick or pinch were absent. Self-mutilation limited to the distal digits appeared on the first or second postoperative days and then progressed proximally. The forelimbs were symmetrically affected, and no other body parts were mutilated. The spatial precision of this syndrome, in the absence of visual as well as peripheral somatosensory information from the affected limb, indicates that controlled guidance of the behavior arises from an existing central representation of the limb and its relationship with the total body; a phantom limb. Consideration of other reports regarding the deafferentation syndrome leads to the view that it is motivated by disturbing abnormal sensations (pain) of central neural origin.

Naloxone inhibits and morphine potentiates the adrenal steroidogenic response to ACTH.

The administration of morphine to hypophysectomized rats potentiated the steroidogenic response of the adrenal cortex to exogenous adrenocorticotrophic hormone (ACTH) in a dose-dependent fashion. Conversely, the opiate antagonist naloxone inhibited the adrenal response to ACTH. Naloxone pretreatment also antagonized the potentiating effect of morphine on ACTH-induced steroidogenesis in a dose-dependent manner. Neither morphine nor naloxone, administered to hypophysectomized rats, had any direct effect on adrenal steroidogenesis. These adrenal actions were stereospecific since neither the (+)-stereoisomer of morphine, nor that or naloxone, had any effect on the adrenal response to ACTH. The administration of human beta-endorphin to hypophysectomized rats had no effect on the adrenal corticosterone concentration nor did it alter the response of the adrenal gland to ACTH. These results indicate that morphine can potentiate the action of ACTH on the adrenal by a direct, stereospecific, dose-dependent mechanism that is prevented by naloxone pretreatment and which may involve competition for ACTH receptors on the corticosterone-secreting cells of the adrenal cortex.

Dietary quinine reduces body weight and food intake independent of aversive taste.

Separate groups of rats were chronically fed diets adulterated with either bitter tasting quinine sulfate (QSO4), equal amounts of quinine in the less bitter form of quinine tannate (QT), or an amount of sucrose octaacetate (SOA) determined to have aversive taste properties equal to the QSO4 diet. Dietary adulteration with SOA did not affect food intake or body weight. Dietary adulteration with quinine resulted in an initial reduction in food intake that showed a relative recovery but remained depressed compared to the intake of a group eating a quinine-free diet. Ingestion of diets containing equal amounts of quinine base resulted in equivalent chronic body weight reductions, despite different aversive diet characteristics. These results suggest that bitter taste is not the significant variable underlying the body weight effects of quinine but that quinine exerts some postingestive effect on body weight mediated by a slight but sustained decrease in the level of energy intake.

Inhibition of adrenocorticotrophin secretion during deprivation-induced eating and drinking in rats.

Rats that were maintained on a 23-h food and water deprivation schedule (food and water available between 09:00 and 10:00 h) for 21 days, and whose blood was sampled at various times following initiation of ingestion showed a decrease in plasma adrenocorticotrophin (ACTH) concurrent with dropping plasma levels of corticosterone (COR). This drop occurred from elevated levels of these hormones, most likely due to altered circadian patterns of pituitary-adrenal activity as a result of the rhythm-entraining properties of the feeding schedule. This inhibition of secretion of ACTH is interpreted as reflecting the inhibitory effect of a central nervous system mechanism that can affect ACTH secretion independently of corticosteroid negative feedback.

The effect of pituitary-adrenal function in the modulation of pain sensitivity in the rat.

1. The relationship between adrenalcortical hormones, adrenocorticotrophic hormone (ACTH), and pain sensitivity was investigated in the rat. Pain sensitivity was assessed by measuring paw-lick and jump latencies in response to being placed on a grid at 55 degrees C.2. Bilateral adrenalectomy increased the sensitivity to pain, but adrenal demedullation had no effect.3. Pain sensitivity was inversely related to the circadian changes in circulating corticosterone and was greater at 7 a.m. than at 7 p.m. However, the same variation in pain sensitivity existed if the adrenals were removed, suggesting that the increase in pain sensitivity after adrenalectomy was not related directly to the levels of corticosteriods.4. The time course of the increase in pain sensitivity after adrenalectomy paralleled that of the changes in circulating ACTH. Adrenalectomy markedly increased pain sensitivity at 9 and 18 days following surgery when circulating ACTH levels were markedly elevated and corticosterone was absent, but not at 3 days following adrenalectomy when ACTH levels were lower and corticosterone was absent.5. Hypophysectomy decreased the sensitivity to pain.6. The results indicate that ACTH can alter pain sensitivity and that the effect of corticosteroids on the sensitivity to pain is an indirect one by virtue of their negative feed-back action on the hypothalamic-pituitary system.

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

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

Synaptosomal uptake of hypothalamic monoamines and recovery of pituitary-adrenal activity following medial forebrain bundle lesions in rats.

The normal diurnal variation in plasma corticosterone (COR) was abolished and the response to ether stress was enhanced at 3 days following the production of medial forebrain bundle (MFB) lesions in male rats. However, by 7 days following surgery, basal plasma COR levels and the response to ether stress appeared normal. These alterations and subsequent recovery of pituitary-adrenal activity were accompanied by decreasing hypothalamic synaptosomal uptake of serotonin (5HT) and increasing synaptosomal uptake of dopamine (DA), evident at 3 and continuing at 7 days following the lesion. Uptake of norepinephrine (NE) was not affected at 3 days but showed a reduction at 7 days following surgery. The results suggest that disruption of ascending 5HT and NE fibers to the hypothalamus can alter pituitary-adrenal activity but that normal activity recovers by 7 days following the lesion. The correlation between recovery of pituitary-adrenal activity and increases in the normal uptake of hypothalamic DA suggest that DA may interact with 5HT and NE systems in the normal control of adrenocorticotrophin (ACTH) release.

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

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

Conditioning decreases in plasma corticosterone level in rats by paring stimuli with daily feedings.

This study examined the nature of a stimulus-induced decrease in the plasma corticosterone levels of rats. Rats maintained on a 23-hr food and water deprivation regimen were fed each morning immediately upon entrance of the experimenter into the otherwise isolated animal quarters. After only 14 feeding trials, the rats showed a marked decrease in corticosterone levels within 10 min of the experimenter's entrance whether fed and watered or not. The acquisition of this decrease was then examined over training trials and by comparing the conditioned animals (Group CD) with a group designed to control for pseudoconditioning, sensitization, and habituation (Group PC) during the use of the more distinctive conditioning stimulus of placing the rat's cage in a sound-attenuating chamber. During training. Group CD was fed .5-6 min after placement in the chamber, and Group PC was fed 1.5-2.5 hr before or after placement. After one training trial, the CD and PC groups showed an increase in corticosterone levels in response to chamber placement when not fed or watered. However, after 14 training trials the CD group exhibited a significant decline, whereas the PC group exhibited a rise in corticosterone levels. The results indicate that external stimuli can cause a decrease in corticosterone level by virtue of prior association with feeding and drinking. This strongly suggests an acquired inhibition of the pituitary-adrenal system.