Biomedical subjects

A Shekhar

Publications and source records attributed to A Shekhar.

At least 37 records · Page 2Linked to original sources

PubMed1997

Dissociative symptoms in panic disorder.

The present study examined the prevalence and correlates of dissociative symptoms in patients with panic disorder and patients with other nonpanic anxiety disorders. A total of 56 patients with anxiety disorders (13 with panic disorder alone, 16 with comorbid panic and other anxiety, and 27 with other anxiety disorders) were assessed with structured clinical interviews and a battery of questionnaires. Although 69% of patients with panic disorder experienced depersonalization or derealization during their panic attacks, panic disorder patients were no more likely to experience dissociative experiences as assessed by the Dissociative Experience Scale than patients with other anxiety disorders. In the entire sample, the prevalence of dissociative experiences was very low and well within nonpathological ranges. The correlates of dissociative symptoms were severity of depression, social anxiety, and personality disorders. The implications of these findings for conceptualizing the nature of dissociative symptoms within an anxiety population are discussed.

Adult↗

PubMed1997

Basilar artery response to hyperventilation in panic disorder.

OBJECTIVE: The purpose of this study was to measure the response of basilar artery blood flow to hyperventilation in patients with panic disorder. METHOD: Transcranial Doppler ultrasonography was used to measure basilar artery flow during rest and after hyperventilation in 16 patients with panic disorder and eight normal comparison subjects. The subjects rated their dizziness at each phase. RESULTS: The patients with panic disorder demonstrated greater reduction in flow rates and greater increases in dizziness than the normal comparison subjects. CONCLUSIONS: The greater basilar artery sensitivity to hyperventilation shown by panic disorder patients suggests a possible mechanism for the development of neurological symptoms during panic attacks.

Adult↗

PubMed1997

Excitatory amino acid receptor antagonists block the cardiovascular and anxiety responses elicited by gamma-aminobutyric acidA receptor blockade in the basolateral amygdala of rats.

Blockade of gamma-aminobutyric acid (GABAA) receptors in the anterior basolateral amygdala (BLA) with bicuculline methiodide results in an increase in heart rate, blood pressure and "anxiety" in rats. Glutamate receptors in the BLA are also reported to be involved in eliciting anxiety responses. The purpose of this study was to investigate the interaction between GABAergic inhibition and glutamatergic excitation in the BLA. Male Wistar rts were implanted with femoral arterial catheters and bilateral chronic microinjection cannulae into the BLA. Each animal was injected with either artificial cerebrospinal fluid (100 nl), bicuculline methiodide (10 pmol/100 nl) or bicuculline methiodide + one dose of an antagonist of either the N-methyl-D-aspartate receptor [AP5 (20 and 100 pmol) and dizocilpine (25 and 125 pmol)] or the non-N-methyl-D-aspartate ionotropic receptor [CNQX (10 and 50 pmol) and GYKI 52466 (50 and 250 pmol)]. Increases in heart rate, blood pressure and "anxiety" (as measured in the social interaction test) observed in rats after bicuculline methiodide injections into the BLA were blocked in a dose dependent manner with the concurrent injections of either N-methyl-D-aspartate or non-N-methyl-D-aspartate antagonists, suggesting that activation of both subtypes of glutamate ionotropic receptors may be necessary for the responses elicited by GABAA receptor blockade in the basolateral amygdala.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1996

The effects of GABAA receptor blockade in the dorsomedial hypothalamic nucleus on corticotrophin (ACTH) and corticosterone secretion in male rats.

Experiments were conducted to test if blockade of GABAA receptors in the dorsomedial hypothalamic nucleus (DMH) of rats, which is known to elicit cardiovascular and anxiety responses, would also elicit changes in the plasma levels of adrenocorticotrophic hormone (ACTH) and corticosterone. Male Sprague-Dawley rats were anesthetized with pentobarbital, fitted with femoral arterial catheters and implanted with microinjection cannulae into the DMH or the sites anterior to the DMH (i.e., closer to the paraventricular nucleus (PVN) of the hypothalamus). The rats were then injected with either artificial cerebrospinal fluid (aCSF; 100 nl) or the GABAA antagonist, bicuculline methiodide (BMI; 50 pmol in 100 nl) and their plasma samples obtained at 5, 30, 60, and 120 min after microinjection. Plasma ACTH and corticosterone were measured by using a radioimmunoassay. Rats injected with BMI, but not aCSF, into the DMH showed significant increases in heart rate (HR, 110 +/- 16 beats/min), blood pressure (BP; 30 +/- 4 mmHg), and plasma levels of both ACTH (64 +/- 10 pg/ml) and corticosterone (170 +/- 25 ng/ml) from baseline. BMI injections into the anterior sites closer to the PVN did not elicit significant increases in HR, BP, or plasma levels of ACTH and corticosterone. These results suggest that a tonic GABAA receptor-mediated inhibition system regulates a coordinated physiological and neuroendocrine response in the DMH and that this neuroendocrine response is not due to diffusion of BMI to the PVN of rats.

Adrenocorticotropic Hormone↗

PubMed1996

Prevalence and correlates of anger attacks: a two site study.

Although anger attacks have been described in depressed outpatients, they have not been well studied in other disorders. In Study 1, we examined the prevalence of anger attacks in 50 outpatients with panic disorder. In Study 2, we replicated the initial findings at an independent site and examined the specificity of anger attacks by comparing their occurrence in patients with panic disorder, patients with other non-panic anxiety disorders and patients with a depressive disorder. At both sites, we also explored the relationship between anger attacks and demographic and clinical characteristics, such as gender, presence and severity of depression, and social anxiety measures. In both sites, the prevalence of anger attacks in patients with panic disorder was approximately one-third. However, anger attacks were not unique to panic disorder, with similar rates emerging for patients with other anxiety disorders. Furthermore, patients with depressive diagnoses had twice the prevalence of anger attacks than did anxiety patients. At both sites, those with anger attacks were significantly more depressed and were likely to have either current or past history of major depression. Anger attacks were not associated with social anxiety measures, but were related to cluster B, cluster C and self-defeating personality disorder traits. Our findings support the notion that anger attacks are best conceptualized as an associated feature of depression.

Adolescent↗

PubMed1996

Dorsomedial hypothalamic GABA dysfunction produces physiological arousal following sodium lactate infusions.

Since impairing gamma-aminobutyric acidA (GABAA) receptor-mediated inhibition in the dorsomedial hypothalamus (DMH) of rats elicits a panic-like response, experiments were conducted to test if rats with GABA dysfunction in the DMH would be vulnerable to precipitation of a panic-like response after intravenous sodium lactate infusions. Rats were implanted with unilateral infusion cannula into the DMH which were connected with Alzet minipumps that chronically infused (3.5 nmol/microliter /h) either a-CSF (vehicle), dl-(racemic), l-(active) or d-(inactive) isomers of allylglycine (AG), an inhibitor of GABA synthesis. Another group of rats had l-allylglycine pumps implanted in the paraventricular nucleus of the hypothalamus (PVN) as anatomical controls. Animals were tested in the social interaction (SI) test and given sodium lactate infusions (10 ml/kg/15 min) before Alzet pump implantations and on days 4, 7, and 14 after pump placement. Rats were also tested in the elevated plus-maze on treatment day 4. Chronic impairment of GABA function in the DMH and not PVN resulted in rats being more anxious in the SI test on treatment days 4, 7, and 14 and in the elevated plus-maze on day 4 compared to a-CSF and d-AG infusions. Further, rats with GABA dysfunction in the DMH, and not PVN, exhibited significant increases in heart rate and blood pressure following IV sodium lactate infusions. There were significant decreases in DMH glutamic acid decarboxylase activity and GABA content in rats receiving 7 days of dl-AG or l-AG infusions. These results indicate that chronic reduction of GABA function in the DMH leads to the development of panic-like disorder in this animal model.

Allylglycine↗

PubMed1995

Priming of experimental anxiety by repeated subthreshold GABA blockade in the rat amygdala.

Blockade of GABAA receptor function in the area of the anterior basolateral amygdala of rats elicits physiological (increases in heart rate and blood pressure) and behavioral changes similar to symptoms of human anxiety states. Repeated subthreshold blockade of GABAA receptors in this region appears to result in a long-term 'priming' of these anxiety-like responses. The present study was conducted to characterize the 'priming' of the heart rate and blood pressure responses and to test if these 'primed' animals would show increases in anxiety responses. Male Wistar rats with arterial catheters placed for physiological measurements were implanted with chronic microinjection cannulae in the anterior basolateral amygdaloid nucleus (BLA) under pentobarbital anesthesia. Repeated daily injections of a subthreshold dose of bicuculline methiodide (GABAA receptor antagonist; BMI) into the BLA elicited 'priming' of physiological responses after 3-5 injections and this response was maintained for at least 6 weeks. The primed animals also showed increased anxiogenic responses to GABAA blockade in the BLA. The 'priming' of anxiety responses were clearly elicited before kindling of seizures as measured by EEG. These results suggest that this 'priming' phenomenon may be similar to kindling and long-term potentiation. This could be one potential mechanism for developing pathological emotional responses, such as chronic, high levels of anxiety.

Amygdala↗

PubMed1995

Anxiolytic effects of chlordiazepoxide blocked by injection of GABAA and benzodiazepine receptor antagonists in the region of the anterior basolateral amygdala of rats.

The amygdala is a structure that is often implicated in the regulation of anxiety responses. Many studies have shown that injection of benzodiazepines into the amygdala produces an anxiolytic effect. The present study was undertaken to determine whether the anxiolytic effect of administration of systemic benzodiazepine (chlordiazepoxide) might be blocked by local injection of a benzodiazepine receptor antagonist (flumazenil) or GABAA receptor antagonist (bicuculline methiodide; BMI) into the region of the anterior basolateral amygdala (BLA) of rats using an ethologically based test of anxiety, the social interaction test. Injection of flumazenil or BMI into the BLA of rats was found to reverse the anxiolytic effects of peripherally administered chlordiazepoxide. These results suggest a major role for the BLA in mediating the anxiolytic effects of benzodiazepines.

Amygdala↗

PubMed1995

Dorsomedial hypothalamic GABA regulates anxiety in the social interaction test.

Blockade of GABAA function in the region of the dorsomedial hypothalamus (DMH) of rats is known to elicit a constellation of physiologic responses including increases in heart rate (HR), mean arterial blood pressure (BP), respiratory rate, and plasma catecholamine levels, as well as behavioral responses such as increases in locomotor activity and anxiogenic-like effects as measured in a conflict test and the elevated plus-maze test. The aim of the present study was to test the effects of microinjecting GABAA antagonists bicuculline methiodide (BMI) and picrotoxin, as well as the GABAA agonist muscimol, into the DMH of rats placed in the social interaction (SI) test. Muscimol decreased HR and BP but increased SI, whereas the GABA antagonists increased HR and BP but decreased SI time. Blocking the HR changes elicited by GABAergic drugs injected into the DMH with systemic injections of atenolol and atropine methylbromide did not block their effects on SI.

Animals↗

PubMed1995

Regulation of anxiety by GABAA receptors in the rat amygdala.

Blockade of GABAergic inhibition in the region of the anterior basolateral amygdala (BLA) of rats elicits physiologic changes associated with a defense reaction. The present study was undertaken to determine whether GABA receptors in the BLA might be involved in regulating experimental anxiety using the social interaction (SI) and conflict test. Guide cannulae were stereotaxically implanted bilaterally in the BLA of rats for intracerebral microinjections. In the BLA, injection of the GABAA receptor antagonists bicuculline methiodide (BMI) and picrotoxin (PIC) produced anxiogenic-like effects in the SI paradigm, as did BMI injection using the conflict paradigm. Injection of the GABAA agonist muscimol (MUS) into the central nucleus of the amygdala (Ce) produced anxiolytic-like effects in the SI test. Microinjection of MUS, baclofen (GABAB agonist), 2OH-saclofen (GABAB antagonist) or strychnine (glycine antagonist) into the BLA or BMI into the Ce elicited no change in experimental anxiety as measured by the SI test. These results suggest that endogenous GABA acts tonically at GABAA receptors in the BLA to inhibit anxiety responses.

Amygdala↗

PubMed1995

Serum dopamine beta hydroxylase and maltreatment in psychiatrically hospitalized boys.

Fifty boys, hospitalized on a school-age and an adolescent unit in an intermediate length psychiatric hospital, were studied while off psychoactive medication to determine how serum dopamine beta hydroxylase (DBH) activity varies with different childhood maltreatment experiences. Childhood maltreatment was categorized according to onset (before 36 months old, between 36-72 months old and over 72 months old). Childhood maltreatment groups were compared with a group of psychiatrically hospitalized boys who had neither been abused nor neglected. Boys who were younger than 72 months at age of onset of maltreatment had significantly lower DBH activity than those who had experienced maltreatment later in childhood and those who had not been subjected to abuse or neglect. This difference appeared attributable to the DBH activity of school age (but not adolescent) boys who had been abused/neglected before 72 months. Boys with a principal diagnosis of conduct disorder solitary aggressive type had lower DBH activity than boys without this diagnosis regardless of whether or not they had been maltreated. Low serum DBH may be a biological sequela of maltreatment early in life that correlates with the development of conduct disorder solitary aggressive type in boys.

Adolescent↗

PubMed1995

Depression and generalized anxiety symptoms in panic disorder. Implications for comorbidity.

Questionnaires and clinician rating scales have been used to assess anxious and depressive symptoms among patients with panic disorder, but these methods do not usually evaluate symptoms in the same terms as the standardized criteria of diagnostic interviews. The present study provides data on the prevalence of symptoms of major depressive disorder and generalized anxiety disorder in 64 patients with panic disorder. Symptoms were assessed using DSM-III-R definitional criteria that consider not only the presence and severity of symptoms, but also their duration and pervasiveness. Depressive symptoms that most frequently met definitional criteria for diagnostic significance were fatigue, insomnia, and concentration difficulties. Over 50% of the sample endorsed feelings of tension, irritability, and restlessness. Disturbances in appetite, feelings of worthlessness, and suicidal ideation were found in less than 10% of the nondepressed panic patients. The implications of these findings for conceptualizing the comorbidity among anxiety and depressive disorders are discussed.

Adult↗

PubMed1994

Effects of treatment with imipramine and clonazepam on an animal model of panic disorder.

Tonic GABAergic inhibition in the dorsomedial hypothalamus (DMH) has been shown to regulate a constellation of behavioral and physiological responses that resemble a human panic attack. The present study was aimed at testing if the panic-like response elicited by injecting gamma-aminobutyric acid (GABA) antagonists into the DMH can be blocked by pretreating the animals with the antipanic drugs, imipramine and clonazepam. Rats were fitted with arterial catheters and bilateral chronic microinjection cannulae in the DMH. Their baseline heart rate, respiratory rate, blood pressure and "anxiety" (measured by the social interaction test) responses to injection of the GABAA antagonist bicuculline methiodide (BMI) into the DMH were recorded. After treatment in a double-blind manner with vehicle, imipramine (5 and 15 mg/kg, 7 days), and clonazepam (5 mg/kg, 3 days), the response to BMI microinjection into the DMH was once again recorded. Both imipramine and clonazepam, but not vehicle treatments blocked the BMI response.

Analysis of Variance↗

PubMed1994

Fear-potentiated startle elevates catecholamine levels in the dorsomedial hypothalamus of rats.

The norepinephrine (NE), dopamine (DA), and serotonin (5-HT) systems are thought to be important in the development of anxiety and stress. The dorsomedial hypothalamus (DMH) of rats has been implicated in the regulation of physiological and behavioral responses associated with fear and anxiety. In order to elucidate the interactions between the monoamine systems and the DMH, we studied the effects of subjecting rats to the fear-potentiated startle test, a commonly used test of anxiety in rats, on the NE, DA, and 5-HT levels in the DMH. Rats in the potentiated startle test, but not those exposed to just foot shocks or acoustic startle, showed significantly higher levels of NE and DA in the DMH compared to cage controls. In contrast, foot shocks significantly elevated the 5-HT levels in the DMH.

Animals↗

PubMed1993

GABA receptors in the region of the dorsomedial hypothalamus of rats regulate anxiety in the elevated plus-maze test. I. Behavioral measures.

Gamma-aminobutyric acid (GABA) receptor blockade in the region of the dorsomedial hypothalamus (DMH) elicits a constellation of responses including increases in heart rate, blood pressure, respiration, aversive behavioral responses and experimental anxiety as measured by the 'conflict' test. The aim of the present study was to assess the effects of enhancing and blocking GABA receptors in the DMH of rats placed on the elevated plus-maze test of anxiety. Male Sprague-Dawley rats were implanted with chronic microinjection cannulae in the DMH bilaterally at sites where injection of 50 pmol of the GABAA antagonist bicuculline methiodide (BMI) elicited an increase in heart rate of at least 50 beats/min under anesthesia. After recovery, the responses of these rats were tested on the elevated plus-maze following injections of saline, the GABAA agonist muscimol and the GABAA antagonists BMI and picrotoxin. Injection of muscimol caused a dose dependent 'anxiolytic-like' effect while both BMI and picrotoxin caused increases in the experimental anxiety on the elevated plus-maze. Microinjection of muscimol into other non-cardiostimulatory regions of the hypothalamus did not significantly affect the responding of rats on the plus-maze. These results support the hypothesis that GABAA receptors in a discrete cardiostimulatory region of the DMH regulate experimental anxiety in rats.

Animals↗

PubMed1993

GABA receptors in the region of the dorsomedial hypothalamus of rats regulate anxiety in the elevated plus-maze test. II. Physiological measures.

In the previous report, we had shown that blockade and enhancement of GABAA receptors in the DMH of rats increased or decreased the level of anxiety, respectively, as measured by the elevated plus-maze test. The present study was conducted to assess the effects of enhancing GABAA neurotransmission in the DMH of rats on the physiological concomitants of anxiety such as increases in heart rate (HR), blood pressure (BP) and plasma norepinephrine (NE) levels while the animals were placed on the elevated plus-maze. Male Sprague-Dawley rats were equipped with arterial and venous catheters and stereotaxically implanted with microinjection cannulae in the cardiostimulatory region of the DMH where injection of bicuculline methiodide (BMI) elicited increases in heart rate under anesthesia. After recovery, rats were injected with either saline or the GABAA agonist muscimol and their HR, BP and plasma NE responses were measured when confined in the open or the closed arm of the elevated plus-maze. Injection of muscimol into the DMH reduced the increases seen in HR, BP and plasma NE when the rats were confined to either the closed or the open arms in addition to decreasing 'anxiety' in the plus-maze. Injection of muscimol into the areas of the hypothalamus surrounding the DMH did not significantly affect the changes in HR, BP and plasma NE in the plus-maze. Blocking the changes in HR and BP elicited by microinjecting GABAergic drugs into the DMH of rats, with systemic injections of a combination of atropine and the beta-blocker atenolol, did not block the behavioral effects of the GABAergic drugs in the plus-maze test.

Animals↗

PubMed1993

Anxiety and motor performance in Parkinson's disease.

Previous work has suggested that anxiety disorders are common in patients with Parkinson's disease. To study the relationship between anxiety and response fluctuations in Parkinson's patients further, we compared changes in Spielberger anxiety state scores with changes in parkinsonian disability as determined by the Parkinson's symptom diary (PSD). Anxiety state and PSD scores were obtained in 19 patients with idiopathic Parkinson's disease during on and off periods. Spielberger anxiety state scores were higher during off periods than during on periods (38.8 +/- 12.4 vs. 45.6 +/- 12.4, p < 0.03); further, the magnitude of the change in anxiety state scores was correlated with the change in PSD scores (rs = 0.616, p = 0.006). Spielberger anxiety trait scores were also correlated with disease duration. Our findings support existing data suggesting that anxiety can contribute significantly to morbidity in Parkinson's disease and suggest that anxiety varies with fluctuations in motor performance.

Aged↗

PubMed1991

Blockade of GABAA receptors in the region of the anterior basolateral amygdala of rats elicits increases in heart rate and blood pressure.

Stimulation of the amygdala in rats is known to elicit increases in heart rate (HR) and blood pressure (BP) as well as locomotor activity associated with emotional arousal. The present study was conducted to localize and characterize the role of the GABA system of the amygdala in regulating these cardiovascular responses. Male Sprague-Dawley rats with arterial catheters placed for physiological measurements were implanted with chronic microinjection cannulae in the anterior basolateral (BLA) and central (Ce) amygdaloid nuclei under pentobarbital anesthesia. After recovering, rats were microinjected bilaterally with saline (250 nl) and bicuculline methiodide (BMI, 5-25 ng/250 nl), a selective GABAA antagonist. Microinjection of BMI in the BLA caused significant increases in HR and BP as well as locomotor stimulation while saline had no effect. The cardiovascular response to BMI was blocked by pentobarbital anesthesia. Microinjection of equimolar concentrations of (+)-baclofen HCl (GABAB agonist), phaclofen (GABAB antagonist), or strychnine (glycine antagonist) into the BLA or BMI into the Ce had no significant cardiovascular effects. The cardiovascular effects of BMI injection in the BLA does not appear to be secondary to generalized seizure activity. These results suggest that endogenous GABA, acting on GABAA receptors in the region of the BLA, may be involved in cardiovascular regulation.

Amygdala↗