Biomedical subjects

A Shekhar

Publications and source records attributed to A Shekhar.

44 records · Page 3Linked to original sources

PubMed1991

Low dopamine-beta-hydroxylase: a biological sequela of abuse and neglect?

Twenty-one psychiatrically hospitalized boys were studied while off psychoactive medication to determine if conduct disorder, solitary type, and abuse or neglect experiences correlated with low levels of dopamine-beta-hydroxylase (DBH) activity. Preliminary results supported earlier findings that undersocialized types of conduct disorder in boys were correlated with low DBH activity. Possible or definite neglect or abuse before 36 months of age was correlated with low DBH activity. Abuse or neglect was not correlated with low DBH activity when time of occurrence was not specified. Low serum DBH may be a biological sequela of seriously disrupted attachment.

Adolescent↗

PubMed1990

GABA receptors in the posterior hypothalamus regulate experimental anxiety in rats.

Blockade of gamma-aminobutyric acid (GABA) function in the posterior hypothalamus of rats elicits a pattern of physiological and behavioral arousal consisting of increases in heart rate, respiration and blood pressure as well as intense locomotor stimulation and a selective enhancement of avoidance responding. The present study was conducted to assess the possibility that GABA-mediated neurotransmission in the posterior hypothalamus of the rat may regulate anxiety. Male rats were trained in a 'conflict' schedule consisting of a high and a low intensity of punishment ('high' and 'low' conflict) capable of measuring decreases and increases in the level of 'anxiety', respectively. Guide cannulae were stereotaxically implanted bilaterally in the posterior hypothalamus of these rats at sites where microinjection of bicuculline methiodide (BMI) 25 ng caused increases in heart rate under anesthesia. After recovery, they were tested: (1) in the high conflict schedule after microinjection of saline and two doses of the GABAA receptor agonist muscimol; and (2) in the low conflict schedule after injecting saline, the GABAA receptor antagonists, BMI and picrotoxin, and the glycine antagonist, strychnine. Injection of muscimol caused a significant and selective anti-conflict effect while both BMI and, at appropriate doses, picrotoxin produced pro-conflict effects. Microinjection of strychnine into the posterior hypothalamus or muscimol and picrotoxin into the lateral hypothalamus did not influence conflict responding. These results suggest that endogenous GABA acts on GABAA receptors in a discrete area of the posterior hypothalamus to regulate the level of experimental anxiety in rats.

Animals↗

PubMed1989

Anxiogenic effects of noreleagnine, a water soluble beta-carboline in rats.

We tested noreleagnine, a beta-carboline which unlike other beta-carbolines remains in aqueous solution at physiological pH, as well as chlordiazepoxide, a traditional benzodiazepine, and their interaction with the benzodiazepine receptor antagonist R0 15-1788 in a modified approach schedule with two levels of conflict. Noreleagnine displayed pro-conflict activity characteristic of beta-carbolines and chlordiazepoxide elicited an anti-conflict effect, both of which were blocked by pretreatment with R0 15-1788. We believe this to be the first clear demonstration that noreleagnine has an anxiogenic effect and that this effect is mediated by its action on benzodiazepine receptors.

Animals↗

PubMed1988

Response suppression in rats after bilateral microinjection of 5-hydroxytryptophan in lateral hypothalamus.

Studies using the 5-hydroxytryptophan (5-HTP) animal model of depression have led to the development of the hypersensitive postsynaptic serotonin receptor theory of depression. To demonstrate more clearly that the 5-HTP-induced suppression is a centrally mediated phenomenon, rats were implanted with bilateral cannulae in the lateral hypothalamus and received microinjections of D,L-5-HTP (100-500 ng) 15 min after the start of a VI operant session (milk reinforcement). Significant decreases in responding were observed that were comparable to those obtained after a systemic injection of 50 mg/kg D,L-5-HTP. Rats receiving a microinjection of 5-HTP in the posterior hypothalamus did not exhibit a behavioral effect. Rats working on shock-avoidance schedules did not demonstrate response suppression following microinjection of 5-HTP into the lateral hypothalamus, which is the same result as that following systemic 5-HTP administration. These data support the important role previously assigned to central 5-HT mechanisms in the 5-HTP animal model of depression.

5-Hydroxytryptophan↗

PubMed1987

Selective enhancement of shock avoidance responding elicited by GABA blockade in the posterior hypothalamus of rats.

Recent studies have shown that blockade of gamma-aminobutyric acid (GABA) in the posterior hypothalamus in anesthetized rats elicits cardio-respiratory stimulation similar to that seen in emotional defense reactions and, in conscious rats, locomotor arousal suggesting a flight response. The present study was conducted in order to test the hypothesis that the behavioral effects elicited by GABA blockade in the posterior hypothalamus were the results of disinhibiting a mechanism whose activation selectively enhances reactivity to aversive stimuli. Male rats were trained on a Sidman shock avoidance schedule (RS20:SS10) as well as a food-reinforced approach schedule (VI 1). Under anesthesia, guide cannulae were stereotaxically implanted bilaterally in the posterior hypothalamus at sites where microinjection of the GABA antagonist, bicuculline methiodide (BMI) 25 ng, increased heart rate. After recovery, rats were tested in both the avoidance and VI 1 schedules after hypothalamic microinjection of saline, BMI 25 ng, and the GABA agonist, muscimol 25 ng. Microinjection of BMI significantly increased the avoidance responses but had no effect on the approach responses. Muscimol decreased both the avoidance and approach responses. When microinjected into the lateral hypothalamic area, BMI had no effect on the response rates in either schedule while muscimol decreased the approach responding only. Therefore, GABA blockade at the discrete area of the posterior hypothalamic nucleus appears to elicit a selective enhancement of avoidance responses. These results suggest that an endogenous GABAergic system in the posterior hypothalamus may tonically inhibit a constellation of autonomic, locomotor and motivational responses that are necessary for some types of defense reaction.

Animals↗

PubMed1987

Defense reaction elicited by injection of GABA antagonists and synthesis inhibitors into the posterior hypothalamus in rats.

Blockade of gamma-aminobutyric acid (GABA) in the posterior hypothalamic nucleus elicits cardiorespiratory stimulation in anesthetized rats. The present study was conducted to test the hypothesis that blockade of GABA in this cardiostimulatory area of the posterior hypothalamus in conscious animals would elicit a defense reaction characterised by a "fight or flight" response. Blockade of GABA was achieved by injecting bicuculline methiodide (BMI 1-25 ng) and picrotoxin (4-100 ng), two post-synaptic GABA antagonists and isoniazid (INH 35 and 70 micrograms), an inhibitor of the synthesis of GABA, bilaterally into the posterior hypothalamus through chronically implanted microinjection cannulae. All three drugs produced dose-dependent increases in locomotor activity, suggesting an "escape" reaction which was quantified as number of crossings and rearings. The effects of bicuculline and picrotoxin appeared immediately after the injection while those of isoniazid appeared much more slowly, attaining peak effects 24 +/- 1 min after injection. Injection of either strychnine (38 ng) into the posterior hypothalamus or bicuculline into the lateral hypothalamic area (LHA) or the dorso-medial/ventro-medial hypothalamus (DMH/VMH) did not elicit a significant increase in locomotor behavior. These results suggest that both the physiological and locomotor components of the hypothalamic defense reaction may be under tonic GABAergic inhibition in the region of the posterior hypothalamus.

Aggression↗

PubMed1987

Role of GABAergic mechanisms in the central regulation of arterial pressure.

Gamma aminobutyric acid (GABA) may represent the single most prevalent neurotransmitter in the mammalian central nervous system. Consequently, it should come as little surprise that the neural circuitry concerned with regulating systemic arterial pressure through the autonomic nervous system utilizes a number of GABAergic inhibitory mechanisms which are anatomically and functionally distinct. This article will, first, summarize findings from our laboratory and other which suggest some of these roles in the mammalian brainstem, and, second, trace a line of research pointing to a particular GABAergic inhibitory mechanism in the forebrain that may have some relevance to experimental and human hypertension.

Animals↗

PubMedDate not supplied

Evaluating and treating anxiety disorders in medical settings.

Anxiety disorders and medical illness present to the primary care physician as a common comorbidity. This article aims to review the literature on the prevalence of anxiety disorders in patients presenting to primary care physicians; to address the key issues in assessing the comorbid condition; and to discuss psychological and pharmacological treatment options for patients with a comorbid anxiety disorder and medical illness. Anxiety disorders are highly prevalent within the primary care population, and these disorders significantly impact the patient's course and outcome. Fortunately, primary care physicians have a variety of effective cognitive, behavioral and pharmacological interventions available for managing these patients with comorbid anxiety and medical illnesses.

Anti-Anxiety Agents↗