Maurice G. King

Parameters of novelty, shock predictability and response contingency in corticosterone release in the rat

Abstract Exposure of male C.S.F. rats to novel apparatus raised plasma corticosterone levels, but the effect habituated. Two aspects of shock predictability were studied: temporal regularity vs irregularity of shock and presence or absence of a warning signal. Irregular shock produced a greater corticosterone response than regular shock but only if both were signalled. The addition of an escape contingency to a signalled, irregular shock resulted in lowered escape latency but no corresponding change in corticosterone levels occurred. In most experimental treatments in which shock was used the corticosterone levels did not habituate even after 4 days of treatment. The results were discussed in terms of: (i) role of psychological component in psychosomatic stress, (ii) the conflict of data between behavioural and physiological measures of aversiveness, and (iii) possible neuroendocrine pathways in psychological stress.

Melatonin: Effects on brain and behavior

Abstract The rat pineal, weighing about 1 mg, contains cells called pinealocytes and astrocytes, and secretes a family of methoxyindoles of which melatonin (N-acetyl-5-methoxytryptamine) is the most potent known substance. The pineal receives both blood and neural input and the synthesis of melatonin seems to be controlled by light/dark conditions, the highest levels being synthesized and secreted in the middle of the dark period and the lowest levels being generated in the middle of the light period. After the structural identification of melatonin by Lerner, it has been demonstrated that melatonin affects the release of MSH from the rat pituitary and MIF-I from the hypothalamus and that conversely melatonin release is also affected by circulating MSH and MIF-I. Melatonin is known to be derived from N-acetylated 5-HT by the action of NE release in the pineal cells in the dark phase causing an enzymatic (NAT) action. The N-acetyl-5-HT is then O-methylated by the action of HIOMT (which increases in the dark) leading to the formation of melatonin. Melatonin and MSH seem to have antagonistic effects on various physiological and behavioral functions. Melatonin lightens frog skin as opposed to the darkening effect of MSH. Melatonin induces sleep in cats, chicken and humans and also lengthens the pentobarbitone-induced sleep in animals. The behavioral effects of melatonin also include decreased motoric activity, decreased defecation, and facilitated extinction (inhibition of memory) of an AAR and of a PAR. However, subsequent studies could not establish an effect of melatonin on activity, but demonstrated a significant effect of melatonin on stress response inhibition. The role of central CAs, mainly DA (besides 5-HT) seems to be implicated in melatonin-induced inhibition of stress responses (indexed by reduced plasma 11-OHCS and novelty-induced defecation). Melatonin-induced facilitation of the extinction of learned responses may be related to the observed rise in brain CAs and 5-HT after melatonin administration over days. However, the action of melatonin is thought to be inseparable from the actions of other neuropeptides (e.g., MSH, MIF-I or AVT) and central neurotransmitters (e.g., 5-HT, GABA, and NE).

Adaptation of the glucocorticosterone response to novelty

Abstract The 11-hydroxycorticosterone (11-OHCS) response in male rats to novelty as a stressor was examined. Since the emphasis to date has been on short durations of exposure to novel stimuli, up to 45 min only, the present study aimed at investigating the elevation and adaptation of the 11-OHCS response to prolonged exposure to novel environments. It was found that the 11-OHCS elevation due to a novel environment takes about 4 hr to return to resting levels. Net elevations of 11-OHCS induced by novelty in the rat appear to be affected by the underlying circadian rhythm. In addition such elevations due to novelty are not constant over time but are subject to a ceiling effect.

Pavlovian conditioning of nasal tryptase release in human subjects with allergic rhinitis.

The role of Pavlovian conditioning in humans with perennial allergic rhinitis was investigated using release of tryptase from sensitised mast cells as an indicator of allergic responsiveness. Challenge with house dust mite allergen (unconditioned stimulus) was paired with a drink of novel taste and appearance (conditioned stimulus) in a single conditioning trial. Upon reexposure to the conditioned stimulus alone, levels of mast cell tryptase released in subjects who had received both the novel drink and allergen challenge on the conditioning trial was significantly greater than subjects who had received either the drink or the allergen alone. The results support the involvement of the central nervous system in mast cell degranulation in allergic rhinitis in humans.

Systemic administration of Met-enkephalin, (D-Ala2)-Met-enkephalin, β-endorphin, and (D-Ala2)-β-endorphin: Effects on eating, drinking and activity measures in rats

Rats were given four daily, interperitoneal injections (80 μg/kg) of Met-enkephalin, (D-Ala2)-Met-enkephalin-NH2, β-endorphin, (D-Ala2)-β-endorphin or the diluent (0.9% NaCl acidified to, 0.01 M with acetic acid). Animals were subsequently tested for food and water intake and activity. Met-enkephalin injections did not affect any of the measures but its (D-Ala2) analog reduced food intake and some of the activity measures in a complicated way. β-Endorphin injections did not affect food or water intake; in familiar situations these animals were less active while novel situations seemed to potentiate activity. The (D-Ala2) analog reduced wheel running over 24 hours.

Behavioral conditioning prolongs heart allograft survival in rats

Conditioned immunosuppression using a taste aversion paradigm has been demonstrated in a number of laboratory models but few reports have demonstrated changes in immunity sufficient to be of clinical relevance. The experiments reported here demonstrate that the survival of heart allografts in rats can be prolonged by behaviorally conditioned immunosuppression using cyclosporin A (CsA) as an unconditioned stimulus in taste aversion conditioning. Conditioned animals received saccharin as the conditioned stimulus paired with an injection of CsA at 10 and 6 days prior to transplantation. They were reexposed to saccharin alone 1 day prior to and 3 days after transplantation. On these occasions the conditioned group displayed taste aversion behavior when offered saccharin and a significant prolongation of heart graft survival was observed compared to the conditioned and nonconditioned control groups. These experiments suggest that behaviorally conditioned immunosuppression may have important clinical implications as an adjunct to drug treatments in transplantation medicine.

Catecholamines and aversive learning: A review

Experimental evidence is reviewed for the implication in aversive learning of the catecholamines, in particular noradrenaline and dopamine and the pituitary-adrenocortical system, in particular adrenocorticotrophic hormone and corticosterone. Depending on task difficulty peripheral neural noradrenaline may be an important factor in aversive learning whereas brain catecholamines are important regardless of task difficulty. The adrenocortical system, as indexed by plasma levels of corticosterone, is also implicated in complex aversive tasks. To date, no convincing empirical evidence exists for a link mechanism between the brain catecholamine system and the adrenocortical system following aversive learning. Earlier behavior theories of aversive learning are reformulated in the light of more recent findings on neuroregulation.

A Minnesota Multiphasic Personality Inventory profile of women with allergic rhinitis.

&NA; The aim of this study was to explore relationships among perennial allergic rhinitis and personality traits in a nonpsychiatric female population of proven allergic status. Female subjects were assigned to the allergic (N = 22) or nonallergic group (N = 18) on the basis of skin prick test and self‐reported allergic status. Analysis of MMPI profiles showed that allergic subjects scored significantly higher on the Hypochondriasis (Hs) and Social Introversion (Si) scales and significantly lower on the Correction (K) and Ego Strength (Es) scales. The results suggested that women with perennial allergic rhinitis show poorer psychological functioning than nonallergic women. In addition, the number of allergies was positively correlated with T scores on the Hs, Depression (D), Hysteria (Hy), Psychasthenia (Pt), Schizophrenia (Sc), Si, and Conscious Anxiety (A) scales, and negatively correlated with T scores on the K and Es scales. Skin reactivity to house dust mite and grass pollen allergens were positively correlated with scores on Si, whereas skin reactivity to grass pollen and mold allergens was positively correlated with D and Pt (grass) and Pd and Sc (grass and mold). Two possible mechanisms explaining the link between psychological factors and allergic rhinitis include (1) the effect of cortisol on IgE production or (2) the production of mediators during an allergic reaction which travel from the nose to the brain.

In vivo effects of β-endorphin on lymphocyte proliferation and interleukin 2 production

Abstract Experiments were undertaken in rats to investigate the effects of in vivo infusion of β-endorphin (BEP) on subsequent Con A-induced proliferation and interleukin 2 (IL-2) production by spleen cells in vitro . BEP administration induced a dose-dependent enhancement of the proliferative response to Con A. Infusion of the opiate antagonist naloxone (NAL) inhibited the Con A response and infusion of NAL prior to BEP resulted in even further inhibition. None of these treatments resulted in detectable alterations in IL-2 production after 48 h in culture. To demonstrate a direct interaction between BEP and lymphocytes, spleen cells were incubated in vitro with varying concentrations of BEP and/or NAL. Enhanced Con A-induced proliferation was observed following incubation with BEP in the range 10 −12 to 10 −9 M (levels comparable to the effective in vivo doses) and this effect was abrogated by NAL pretreatment (10 −6 M ). These data indicate a role for BEP in enhancing lymphocyte reactivity which is to some extent dependent on opiate receptors on the cell surface. This report extends the evidence obtained from in vitro experiments implicating endogenous opioids in modulation of host immunity by demonstrating that these effects can be obtained in vivo .

Effects of melanocyte-stimulating hormone (MSH) and melatonin on passive avoidance and on an emotional response.

The present experiment investigated the opposite effects of synthetic alpha-MSH and Melatonin on acquisition and extinction of a passive avoidance response (PAR) and on emotionality, as indexed by defecation, in the PA box. It was found that intraperitoneal (IP) administration of alpha-MSH delayed extinction and increased defecation responses whereas IP administration of Melatonin facilitated extinction of the PAR and decreased defecation. The present experiment confirmed MSH-Melatonin opposition on memory and on the defecation response.