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C W Berridge

Publications and source records attributed to C W Berridge.

14 recordsLinked to original sources
PubMed1991

Individual differences in behavioral measures: correlations with nucleus accumbens dopamine measured by microdialysis.

Rats were placed in one of two novel test environments for behavioral observation. In one, exploratory behavior (assessed by hole pokes) and locomotion were assessed during a 10-min test session. In the other, the chewing of varied objects on the cage floor was rated over a 20-min session. Within 2-18 days, animals were anesthetized and microdialysis probes were implanted into the nucleus accumbens for measurement of basal and d-amphetamine-stimulated levels of dopamine (DA). These measures were then correlated with the individual behavioral rating collected earlier from the drug-free animals. We found a significant correlation between duration of exploratory behavior and amphetamine-induced DA release. Locomotor activity did not correlated with either basal or amphetamine-stimulated DA release. Duration of chewing episodes correlated with basal levels of DA, as well as with amphetamine-induced DA release. Our studies indicate that differences in the dopaminergic responsivity of the nucleus accumbens (or other circuitry influencing nucleus accumbens DA function) may contribute to individual differences in certain behaviors displayed by the animals when placed in a novel environment.

Amphetamine↗
PubMed1991

Electrophysiological evidence for the involvement of the locus coeruleus in alerting, orienting, and attending.

In this chapter, we describe recent observations from our laboratory which support the thesis that the locus coeruleus (LC), via its massively divergent efferent projections, participates in generating a generalized brain state that can be characterized as "alertness." The first of these observations suggests that LC activation can convert the electroencephalographic (EEG) activity of the forebrain from patterns characteristic of a non-alert state to those characteristic of an alert state. The second observation indicates that LC activation alters sensory responses of individual neocortical neurons in a way that is compatible with the general thesis presented here, suggesting that LC-induced alterations in cortical neuronal activity may be an integral component of a hypothesized participation of the LC in cortically mediated attentional processes. The third observation indicates that LC may modulate forebrain components of orienting responses that are indexed by event-related potentials (ERPs). Thus, the experiments described below involve electrophysiological assessment of forebrain information processing at three different levels of organization: activity of individual neurons in the millisecond range, neuronal ensemble activity persisting for 10-200 msec as indexed by ERPs, and ensemble/regional activity sustained for seconds to minutes as indicated by EEG measures. These observations suggest that alterations induced in forebrain function by manipulations of LC activity are evident at all three of these levels.

Animals↗
PubMed1991

Effects of locus coeruleus activation on electroencephalographic activity in neocortex and hippocampus.

Experiments were conducted to examine the hypothesis that increased neuronal discharge activity of noradrenergic neurons of the locus coeruleus (LC) above resting discharge rates can alter forebrain electroencephalographic (EEG) activity. Small infusions (70-135 nl) of the cholinergic agonist bethanechol within 500 microns of the LC were used to activate this nucleus reversibly in halothane-anesthetized rats. A combined recording-infusion probe allowed verification of this electrophysiological activation. Simultaneously, EEG activity was recorded from sites in the frontal cortex and hippocampus and subjected to power-spectrum analyses. The findings were (1) LC activation was consistently followed, within 5 to 30 sec, by a shift from low-frequency, high-amplitude to high-frequency, low-amplitude EEG activity in frontal neocortex and by the appearance of intense theta-rhythm in the hippocampus; (2) forebrain EEG changes followed LC activation with similar latencies whether infusions were made lateral or medial to the LC; (3) infusions placed outside the immediate vicinity of the LC were not followed by these forebrain EEG effects; (4) following infusion-induced activation, forebrain EEG returned to preinfusion patterns with about the same time course as the recovery of LC activity (10-20 min for complete recovery). These infusion-induced effects on EEG activity were blocked or severely attenuated by pretreatment with the alpha 2-agonist clonidine, which inhibits LC discharge and norepinephrine release, or the beta-antagonist propranolol. These observations indicate that enhanced LC discharge activity is the crucial mediating event for the infusion-induced changes in forebrain EEG activity observed under these conditions and suggest that LC activation may be sufficient to induce EEG signs of cortical and hippocampal activation.

Animals↗
PubMed1990

DSP-4-induced depletion of brain norepinephrine produces opposite effects on exploratory behavior 3 and 14 days after treatment.

Exploratory behavior of a complex novel environment was examined 3 and 14 days following treatment with the noradrenergic-selective neurotoxin, DSP-4. This toxin significantly decreased norepinephrine concentrations in neocortex and hippocampus but not hypothalamus. DSP-4 significantly increased exploratory behavior in animals tested 3 days after treatment. In contrast, exploratory behavior was decreased in animals tested 14 days after treatment. The effect of DSP-4 at 3 days is similar to treatments that act to inhibit noradrenergic function such as administration of the alpha 1-antagonist, prazosin, or the alpha 2-agonist, clonidine. The effect of DSP-4 at 14 days resembles that observed following treatment with the alpha 1-agonist, phenylephrine, or the alpha 2-antagonist, idazoxan. These data provide additional support for a role of noradrenergic systems in exploratory behavior. The simplest explanation for the time dependent effects of DSP-4 on exploratory behavior is the occurrence of the slow development of a supersensitivity of cerebral systems affected by norepinephrine.

Animals↗
PubMed1990

Corticotropin-releasing factor acts via a third ventricle site to reduce exploratory behavior in rats.

Corticotropin-releasing factor (CRF, 20-25 ng) injected into the lateral or fourth ventricles of rats decreased exploratory behavior in the multicompartment testing chamber (MCC), as assessed by decreased mean contact times with novel stimuli. This result extends similar observations made previously in mice. To investigate the site of this action of CRF, cold cream plugs injected into the cerebral ventricles of rats were used to prevent access of the CRF to specific periventricular sites. When the cerebral aqueduct was blocked with cold cream, CRF injected into the lateral ventricle, but not the fourth ventricle, decreased exploratory behavior in the MCC. These results suggest that CRF does not act in the fourth ventricle to alter behavior in the MCC, and most likely acts in the lateral or third ventricles. Cold cream blocks within the third ventricle prevented the effect of lateral ventricle administration of CRF. The clearest effects were obtained when the anteroventral portion of the third ventricle (AV3V) had been coated with cold cream. This region, which contains the organum vasculosum laminae terminalis (OVLT), was the only region blocked that showed a significant statistical interaction between the cold cream block and the effect of CRF. This result suggests that the OVLT, or regions close to it, is the primary site of the behavioral action of CRF in the MCC. It is possible that the peptide could be taken up in this region and transported to another brain site.

Animals↗
PubMed1989

CRF and restraint-stress decrease exploratory behavior in hypophysectomized mice.

Corticotropin-releasing factor (CRF) and restraint-stress both decrease exploratory behavior in rats and mice. The involvement of pituitary-adrenal hormones in eliciting these behavioral effects was examined using hypophysectomized mice. Forty minutes of restraint decreased exploratory behavior in hypophysectomized mice just as it did in intact animals. Similarly, CRF (50 ng) injected into the lateral cerebral ventricles of hypophysectomized mice decreased exploratory behavior. Therefore, the restraint- and CRF-induced decreases of exploratory behavior are apparently independent of the activation of ACTH secretion from the pituitary. It seems likely that CRF acts intracerebrally to elicit this effect of restraint, especially because a CRF antagonist can reverse the effects of restraint.

Animals↗
PubMed1989

Restraint-stress-induced changes in exploratory behavior appear to be mediated by norepinephrine-stimulated release of CRF.

Exploratory behavior, measured by the time an animal spends investigating objects in a novel environment, has been shown to be sensitive to prior exposure of the animal to stressors. Using this paradigm, it was demonstrated previously that both corticotropin-releasing factor (CRF) and the alpha 2-adrenoreceptor antagonist, idazoxan, elicited stress-like decreases in exploratory behavior. Because an activation of cerebral noradrenergic systems is observed during stress, following intracerebroventricular (i.c.v.) administration of CRF, or following peripheral administration of idazoxan, the involvement of noradrenergic systems in the behavioral effect of restraint and CRF was examined. Inhibition of norepinephrine (NE) release using the alpha 2-agonist clonidine (25 micrograms/kg, i.p.) or the noradrenergic-selective neurotoxin DSP-4 antagonized the restraint-induced decrease in exploratory behavior. The combination of these 2 treatments completely prevented this effect of restraint. The alpha 1-receptor antagonist prazosin (200 micrograms/kg) also prevented the behavioral effect of restraint, whereas the alpha 1-agonist phenylephrine (50 or 100 ng, i.c.v.) decreased exploratory behavior. None of these treatments consistently altered locomotor activity as measured by the number of entries into the different compartments or the number of rears. These results implicate noradrenergic systems in the stress-related changes in this behavior, consistent with our parallel measures on the production of NE catabolites. Thus, both CRF and noradrenergic systems appear to be involved in the effect of restraint on exploratory behavior in this task. Neither DSP-4 nor prazosin had any effect on the CRF-induced decrease in exploratory behavior. However, the CRF antagonist alpha-helical CRF (20 micrograms, i.c.v.) reversed the decrease in exploratory behavior induced by phenylephrine. The most likely explanation is that the 2 systems act in tandem such that noradrenergic systems regulate the release of brain CRF via an alpha 1-adrenoreceptor. This arrangement parallels that involved in the release of hypothalamic CRF to activate the pituitary-adrenal axis. The implications of these results for research on stress-related behaviors and for the etiology of depression are discussed.

Animals↗
PubMed1987

A corticotropin-releasing factor antagonist reverses the stress-induced changes of exploratory behavior in mice.

Corticotropin-releasing factor (CRF) administered intracerebroventricularly (ICV) to rats and mice has been shown to elicit a variety of behaviors resembling those that occur in stress. In a novel multicompartment chamber, ICV CRF altered the behaviors in a manner closely resembling that observed following a period of restraint. In particular, 75 ng CRF ICV or 30-40 min restraint markedly reduced the time mice spent in contact with novel stimuli. ICV injections of a peptide antagonist of CRF, alpha-helical CRF9-41 (ahCRF), reversed the effects of restraint on this measure. This effect of ahCRF was dose dependent, with a minimal effective dose of 10 micrograms. Other behavioral measures appeared normal, and ahCRF did not significantly alter the stimulus-contact time in unrestrained mice. These results provide strong evidence to support the hypothesis that endogenous CRF may be a factor affecting stress-induced changes in exploratory behavior in mice.

Animals↗
PubMed1987

Corticotropin-releasing factor administration elicits a stress-like activation of cerebral catecholaminergic systems.

The cerebral content of the biogenic amines, dopamine (DA), norepinephrine (NE), and serotonin (5-HT) and their catabolites 30 min after CRF or saline injections was determined using HPLC with electrochemical detection. Injection of CRF (1.0 micrograms) into the lateral ventricles (ICV) of mice produced a behavioral activation in which their motor movements appeared as bursts of activity followed by periods of immobility. CRF administration (ICV or SC) did not alter the concentrations of DA, NE, tryptophan, 5-HT, or 5-hydroxyindoleacetic acid (5-HIAA) in any brain region measured. ICV CRF increased the concentrations of dihydroxyphenylacetic acid (DOPAC), the major catabolite of DA, and of 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG), the major catabolite of NE, in several brain regions. DOPAC:DA ratios were consistently increased in prefrontal cortex, septum, hypothalamus, and brain stem relative to animals injected with saline. MHPG:NE ratios were also increased in the prefrontal cortex and hypothalamus, with a marginal effect (p = 0.06) in brain stem. SC CRF significantly increased DOPAC:DA in prefrontal cortex, and MHPG:NE in prefrontal cortex, hypothalamus and brain stem. Pretreatment with naloxone did not prevent any of the neurochemical responses to ICV CRF, but naloxone alone increased DOPAC:DA in medial profrontal cortex, and decreased MHPG:NE in nucleus accumbens in CRF-injected mice. These results suggest that administration of CRF either centrally or peripherally induces an activation of both dopaminergic and noradrenergic systems in several regions of mouse brain.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Corticotropin-releasing factor elicits naloxone sensitive stress-like alterations in exploratory behavior in mice.

A multicompartment chamber was used to study the investigatory behavior of mice in a novel environment. Restraint stress, subcutaneous morphine (1.75 mg/kg), and ICV corticotropin-releasing factor (CRF; 75 ng) each produced a decreased mean time per contact with novel stimuli. The effect of all three treatments was antagonized by a dose of naloxone that by itself had no significant behavioral effects (0.7-0.75 mg/kg). Naloxone alone at a higher dose (1.25 mg/kg), increased the mean time per contact with the stimuli. These results confirm previous reports of the effects of opiates and stress on this behavior in rats. The similarity of the effects of CRF and stress on the behavioral response to this chamber supports the possibility that CRF may act in the central nervous system to mediate certain behavioral responses in stress.

Animals↗
PubMed1986

Changes in plasma corticosterone and cerebral biogenic amines and their catabolites during training and testing of mice in passive avoidance behavior.

Concentrations of cerebral biogenic amines and their catabolites, and of plasma corticosterone were determined 10 min after training and testing of passive avoidance behavior in mice. Training and testing of mice that had acquired the task well resulted in statistically significant increases of plasma corticosterone, of the DOPAC:DA ratio [an index of dopamine (DA) metabolism] in prefrontal cortex, and of MHPG:NE ratios [an index of norepinephrine (NE) metabolism] in hypothalamus and brain stem. There were also decreases of NE in hypothalamus and brain stem, and an increase of 5-HIAA:5-HT [an index of serotonin (5-HT) metabolism] and of tryptophan in brain stem. Some of these changes also occurred in mice merely exposed to the apparatus but not trained. Plasma corticosterone concentrations were significantly higher in mice that performed the task well compared to those that did not, and there were significant correlations between this measure and the avoidance performance. Although there was only one statistically significant correlation between a cerebral metabolite and the avoidance performance (a decrease in hypothalamic NE), there were indications of relationships between cerebral biogenic amine metabolism and the performance. The patterns of neurochemical and endocrine changes closely resemble those previously observed in response to various stressors. Thus, the changes could reflect stress responses, which may or may not be related directly to the performance of the avoidance task.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

CRF-induced excessive grooming behavior in rats and mice.

We studied the grooming response to lateral ventricle injection of CRF in both rats and mice under similar conditions. One microgram of CRF ICV induced a pronounced increase (3- to 4-fold) in the frequency of self-grooming in rats, but only a much smaller (less than 20%) increase in mice. The minimum effective dose of CRF in rats was 300 ng. Although ACTH1-24 induced less grooming in mice than in rats, the difference in potency did not appear to be sufficient to explain the differences between the effectiveness of CRF in the two species. Whereas ACTH increased all types of grooming scored. CRF increased all forms of grooming except flank scratching with the hind limb. The major effect of CRF was to increase the number of episodes of grooming, whereas ACTH1-24 tended to prolong the length of individual episodes. The excessive grooming induced by ICV CRF was not affected by prior treatment with dexamethasone, suggesting that the increased grooming was not due to secondary release of ACTH from the pituitary. Nevertheless, ICV CRF might induce grooming by releasing MSH/ACTH from cerebral storage sites. CRF-induced grooming, like ACTH-induced grooming, was inhibited by naloxone pretreatment. Despite the small qualitative differences, CRF-induced grooming could be due to secondary release of ACTH.

Animals↗