Stress-induced relapse to drug seeking in the rat: role of the bed nucleus of the stria terminalis and amygdala

There is growing interest in the role that the bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA), components of the extended amygdala, play in drug addiction. Within the BNST and CeA, there is an extensive system of intrinsic, primarily GABAergic, interconnections known to synthesize a variety of neuropeptides, including corticotrophin-releasing factor (CRF). The actions of CRF at extrahypothalamic sites,including the BNST and CeA, have been implicated in stress responses and in the aversive effects of withdrawal from drugs of abuse. Most recently, we have shown a critical role for extrahypothalamic CRF in stress-induced reinstatement of drug seeking in rats. In attempting to determine which brain circuitry mediates the effect of stress on relapse and, more specifically, where in the brain CRF acts to initiate the behaviours involved in relapse, we focused on the BNST and CeA. In the present paper, we summarize studies we have conducted that explore the role of these brain sites in stress-induced relapse to heroin and cocaine seeking, and then consider how our findings can be understood within the more general context of what is known about the role of the BNST and CeA in stress-related and general approach behaviours, such as drug seeking.     

The bed nucleus of the stria terminalis is required for the expression of contextual but not auditory freezing in rats with basolateral amygdala lesions

Previous data suggest that overtraining can overcome fear conditioning deficits in rats with lesions of the basolateral complex of the amygdala (BLA). We have previously shown that the central nucleus of the amygdala (CEA) is essential for the acquisition and expression of conditional fear to both contextual and auditory conditioned stimuli (CSs) after overtraining. This provides strong evidence that the CEA can compensate for the loss of the BLA. Another brain area that may compensate for the loss of the BLA is the bed nucleus of the stria terminalis (BNST). We explored this possibility by examining the consequences of lesions or reversible inactivation of the BNST on the expression of overtrained fear in rats with BLA lesions. We demonstrate that lesions or inactivation of the BNST block the expression of freezing to the conditioning context, but not to an auditory conditional stimulus. These results reveal that the BNST has a critical role in the expression of contextual fear, but not fear to an auditory CS, and is therefore not the essential locus of compensation for fear learning in the absence of the BLA.     

Role of the bed nucleus of the stria terminalis in the cardiovascular responses to acute restraint stress in rats

The aim of this work was to test the hypothesis that the bed nucleus of the stria terminalis (BST) and noradrenergic neurotransmission therein mediate cardiovascular responses to acute restraint stress in rats. Bilateral microinjection of the non-specific synaptic blocker CoCl(2) (0.1 nmol/100 nl) into the BST enhanced the heart rate (HR) increase associated with acute restraint without affecting the blood pressure increase, indicating that synapses within the BST influence restraint-evoked HR changes. BST pretreatment with the selective alpha(1)-adrenoceptor antagonist WB4101 (15 nmol/100 nl) caused similar effects to cobalt, indicating that local noradrenergic neurotransmission mediates the BST inhibitory influence on restraint-related HR responses. BST treatment with equimolar doses of the alpha(2)-adrenoceptor antagonist RX821002 or the beta-adrenoceptor antagonist propranolol did not affect restraint-related cardiovascular responses, reinforcing the inference that alpha(1)-adrenoceptors mediate the BST-related inhibitory influence on HR responses. Microinjection of WB4101 into the BST of rats pretreated intravenously with the anticholinergic drug homatropine methyl bromide (0.2 mg/kg) did not affect restraint-related cardiovascular responses, indicating that the inhibitory influence of the BST on the restraint-evoked HR increase could be related to an increase in parasympathetic activity. Thus, our results suggest an inhibitory influence of the BST on the HR increase evoked by restraint stress, and that this is mediated by local alpha(1)-adrenoceptors. The results also indicate that such an inhibitory influence is a result of parasympathetic activation.     

Posttraining infusion of cholinergic drugs into the ventral subiculum modulated memory in an inhibitory avoidance task: Interaction with the bed nucleus of the stria terminalis

The ventral subiculum (vSUB), a hippocampal efferent target implicated in learning and stress coping, receives cholinergic input and sends glutamatergic output to the bed nucleus of the stria terminalis (BNST). This study examined the roles of vSUB muscarinic activation and its interaction with BNST N-methyl-d-aspartate and noradrenergic receptors in formation of aversive memory. Male Wistar rats with cannulae implanted into the vSUB or BNST were trained on a step-through inhibitory avoidance task. Shortly after training, they received cholinergic drugs infused into the vSUB and/or glutamatergic or noradrenergic drugs infused into the BNST. Results of the 1-day retention tests showed that intra-vSUB infusion of oxotremorine (0.01 μg) or scopolamine (0.3 or 3.0 μg) enhanced or impaired retention, respectively. Both effects were dose- and time-dependent, and 0.001 μg oxotremorine attenuated the amnesia induced by 3.0 μg scopolamine. The oxotremorine-induced memory enhancement was blocked by intra-BNST infusion of dl-2-amino-5-phosphonovaleric acid or propranolol at a dose not affecting retention; the amnesia induced by scopolamine was blunted by intra-BNST infusion of glutamate or norepinephrine at a dose with a negligible effect on retention. These data suggest that in an inhibitory avoidance task muscarinic activation of the vSUB modulated memory formation by interacting with the BNST glutamatergic and noradrenergic functions.     

Post-training infusion of glutamate into the bed nucleus of the stria terminalis enhanced inhibitory avoidance memory: An effect involving norepinephrine

This study examined an interaction between glutamate and norepinephrine in the bed nucleus of the stria terminalis (BNST) in modulating affective memory formation. Male Wistar rats with indwelling cannulae in the BNST were trained on a one-trial step-through inhibitory avoidance task and received pre- or post-training intra-BNST infusion of glutamate, norepinephrine or their antagonists. Results of the 1-day test indicated that post-training intra-BNST infusion of dl-2-amino-5-phosphonovaleric acid (APV) impaired retention in a dose- and time-dependent manner, while infusion of glutamate had an opposite effect. Co-infusion of 0.2 μg glutamate and 0.02 μg norepinephrine resulted in marked retention enhancement by summating non-apparent effects of the two drugs given at a sub-enhancing dose. The amnesic effect of 5.0 μg APV was ameliorated by 0.02 μg norepinephrine, while the memory enhancing effect of 1.0 μg glutamate was attenuated by 5.0 μg propranolol. These findings suggest that training on an inhibitory avoidance task may alter glutamate neurotransmission, which by activating NMDA receptors releases norepinephrine to modulate memory formation via β adrenoceptors in the BNST.     

The orientation anisotropy and orientation constancy: a visual evoked potential study.

Two experiments were conducted on the orientation anisotropy in which averaged visual evoked potentials (VEPs) were recorded from the occipital scalp. The first experiment confirmed the findings of Maffei and Campbell (1970) that obliquely oriented gratings alternated back and forth produced smaller-amplitude VEPs than when the gratings were oriented horizontally or vertically. Since no asymmetry was found in VEPs produced by a Julesz figure presented under identical conditions, it was concluded that direction of displacement could not have been contributing to the effect. In a second experiment head tilt of the subject was manipulated together with grating orientation and the results indicated that the orientation anisotropy is retinally rather than gravitationally referenced. It was concluded that the site of orientation constancy is located either at higher levels of the primary visual system or in the second visual system.     

The Seattle longitudinal study: relationship between personality and cognition

This article reviews the history, measures and principal findings of the Seattle Longitudinal Study. This study began in 1956 focusing upon age differences and age changes in cognitive abilities. Its sampling frame is a large HMO in the Pacific Northwest. The study has been expanded to investigate various influences on cognitive aging including, cognitive styles, personality traits, life styles, and family environment. Current interest is also in the early detection of risk for dementia. In addition, this article reports original analyses of the relation of personality dimensions to cognitive abilities (both concurrent and longitudinal). While personality remains relatively stable over the adult life span, modest proportions of variance are shared between various personality traits and the cognitive abilities.     

Characterizing the time course of an implicature: an evoked potentials study

This work employs Evoked Potential techniques as 19 participants are confronted with sentences that have the potential to produce scalar implicatures, like in Some elephants have trunks. Such an Underinformative utterance is of interest to pragmatists because it can be considered to have two different truth values. It can be considered true when taken at face value but false if one were to treat Some with the implicature Not All. Two accounts of implicature production are compared. The neo-Gricean approach (e.g., Levinson, 2000) assumes that implicatures intrude automatically on the semantics of a term like Some. Relevance Theory (Sperber & Wilson, 1985/1996) assumes that implicatures are effortful and not automatic. In this experiment, the participants are presented with 25 Underinformative sentences along with 25 sentences that are Patently True (e.g. Some houses have bricks) and 25 that are Patently False (e.g. Some crows have radios). As reported in an earlier study (Noveck, 2001), Underinformative sentences prompt strong individual differences. Seven participants here responded true to all (or nearly all) of the Underinformative sentences and the remaining 12 responded false to all (or nearly all) of them. The present study showed that those who responded false to the Underinformative sentences took significantly longer to do so that those who responded true. The ERP data indicate that: (a) the Patently True and Patently False sentences prompt steeper N400's--indicating greater semantic integration--than the Underinformative sentences and that (b) regardless of one's ultimate response to the Underinformative sentences, the N400's were remarkably flat, indicating no particular reaction to these sentences. Collectively, the data are taken to show that implicatures are part of a late-arriving, effort-demanding decision process.     

The relationship between cognitive function and life space: the potential role of personal control beliefs

We examined the relationship of cognitive and functional measures with life space (a measure of spatial mobility examining extent of movement within a person's environment) in older adults, and investigated the potential moderating role of personal control beliefs. Internal control beliefs reflect feelings of competence and personal agency, while attributions of external control imply a more dependent or passive point of view. Participants were 2,737 adults from the ACTIVE study, with a mean age of 74 years. Females comprised 76% of the sample, with good minority representation (27% African American). In multiple regression models controlling for demographic factors, cognitive domains of memory, reasoning, and processing speed were significantly associated with life space (p < .001 for each), and reasoning ability appeared most predictive (B = .117). Measures of everyday function also showed significant associations with life space, independent from the traditional cognitive measures. Interactions between cognitive function and control beliefs were tested, and external control beliefs moderated the relationship between memory and life space, with the combination of high objective memory and low external control beliefs yielding the highest life space (t = -2.07; p = .039). In conclusion, older adults with better cognitive function have a larger overall life space. Performance-based measures of everyday function may also be useful in assessing the functional outcome of life space. Additionally, subjective external control beliefs may moderate the relationship between objective cognitive function and life space. Future studies examining the relationships between these factors longitudinally appear worthwhile to further elucidate the interrelationships of cognitive function, control beliefs, and life space.     

The relationship between disposition and career success: A British study

The relationship of the Five‐Factor Model of personality and general mental ability with extrinsic and intrinsic career success was investigated in a British sample of 308 white‐collar workers. Extrinsic career success was associated with both experiential variables and dispositional variables, while intrinsic career success was almost exclusively associated with personality traits. General mental ability contributed to eventual, but not to organization‐specific extrinsic career success; and neuroticism reduced both extrinsic career prospects and intrinsic career evaluations, while agreeableness reduced extrinsic career prospects but enhanced intrinsic career evaluations. However, in sharp contrast to hypotheses, conscientiousness primarily and extraversion secondarily were negatively associated with extrinsic career success. The findings are discussed with respect to extant knowledge and the British national cultural context.     

The relationship between religion and thought-action fusion: Use of an in vivo paradigm

Research has demonstrated that higher levels of religiosity are positively correlated with thought-action fusion (TAF), a set of cognitive biases found to be associated with obsessive-compulsive symptoms. However, previous studies have exclusively relied on a nomothetic approach to measuring TAF using a single self-report instrument, the thought-action fusion scale. The current study examined the relationship between religiosity and TAF using an in vivo behaviorally-based assessment in which participants thought about and wrote down thoughts of negative events involving loved ones. Forty-three highly religious Protestant Christians were compared to 30 Atheists/Agnostics on their in vivo ratings of anxiety, estimates of likelihood, and moral wrongness related to the negative thoughts. Results indicated that compared to the non-religious participants, those who were highly religious believed that writing and thinking about the negative events was more morally wrong and increased the likelihood of the event. Results are discussed in terms of the potential relationship between certain religious teachings and TAF-related beliefs about the importance, significance, and influence of thoughts.     

The relationship between sex-role orientation and vocational undecidedness: An exploratory study

The relationship between sex-role orientation and vocational choice has attracted empirical interest but many studies conducted have been inconclusive. Giankos and Subich (1986), however, produced a highly significant result (p < .001) which suggested that non-traditionally sex-typed subjects are more vocationally indecisive than traditionally sex-typed subjects. To attempt a replication of this finding, data were collected from 65 subjects, of whom 32 were unemployed and the remaining 33 were in full-time tertiary education. Although statistical analysis revealed no main effect on vocational indecision for either the sex-role identity or unemployed/student distinctions, the data suggested an interaction between these two factors. The level of statistical significance fell between .05 and .10. This trend, together with Gianakos and Subich's finding, suggest that vocational indecision may be associated with an interaction between sex-role orientation and socio-economic factors.     

The effects of lesions in the central nucleus of the amygdala on appetitive classical conditioning in rats

Abstract: Lesions in the central nucleus of the amygdala (cAMY) have been known to interfere with the acquisition of fear classical conditioning when footshock is used as an unconditioned stimulus (US). The present study examined whether or not a similar interference would occur with an appetitive US. Five rats with lesions in the cAMY (the cAMY group), and eight unoperated control rats were trained in an appetitive classical conditioning paradigm, which did not include elements of operant learning, using a visual conditioned stimulus (CS) (5 W of light for 10 s duration) paired with a food pellet US (45 mg, cheese flavor). The behavioral index of appetitive conditioning was an increase in rearing approach behavior to the CS after CS and US pairings. During CS and US pairings, the movement of the rat was limited so that this approach behavior could not occur. As a result, all control rats showed an increase in rearing, but the cAMY group did not. These results suggest that the cAMY is critical for appetitive as well as fear classical conditioning.     

The relationship between state anxiety and depressed mood: A validity study

The validity of the A-State Scale of the State-Trait Anxiety Inventory and the Zung Self-Rating Depression Scale was assessed using data from a general health survey. Depression and anxiety states were found to coexist, however, evidence from a factor analysis, showing items from the two tests loaded on separate factors, demonstrated that these states can be measured independently. Both the A-State and the Zung Scales were found to comprise two factors, and for each scale, one factor consisted of positively phrased items, and the other of negative items. The implications of these findings for the construct validity of the two scales are discussed.     

The temporal distribution of stimulus information in the visual evoked potential

Research in psychophysics (Bloch's law) and perceptual experiments concerned with the integration of successively presented stimuli suggest that the perception of form is a process that occurs over a period of as much as 200-300 msec. Such results prompted the question of whether the visual evoked potential (VEP) might contain information about the distribution over time of perceptual processing. Subjects viewed lines formed from combinations of three lengths and four angles while the EEG was recorded. Analysis of the VEPs indicated that the length and angle of the lines produced temporal distributions of information in the VEP and that the distributions for length and angle were somewhat different. The major difference was that the processing of angle begins earlier and is completed sooner than the processing of length. A conclusion of the experiment was that an alternative or supplement to analyzing VEPs for specific waveform features is to consider the encoding of stimulus information in the VEP as a density or concentration over time.