Biomedical subjects

A Montkowski

Publications and source records attributed to A Montkowski.

23 records · Page 2Linked to original sources

PubMed1995

Chronic infusion of a CRH1 receptor antisense oligodeoxynucleotide into the central nucleus of the amygdala reduced anxiety-related behavior in socially defeated rats.

We studied the role of central amygdala CRH receptors in behavioral responses to an anxiogenic stimulus. An antisense oligodeoxynucleotide corresponding to the rat CRH1 receptor mRNA was infused chronically into the central amygdaloid nucleus of male rats via osmotic minipumps (0.25 micrograms/0.5 microliters/h). Control groups received infusions of either a scrambled sequence oligodeoxynucleotide or vehicle. On the 4th day of treatment, rats were subjected to 10 min of social defeat and immediately afterwards tested on the elevated plus-maze. Antisense oligodeoxynucleotide-treated rats spent significantly more time exploring the open arms of the plus-maze than scrambled sequence- and vehicle-treated animals, both of which did not differ from each other. The social discrimination test, on the other hand, revealed no difference in juvenile recognition abilities among the treatment groups. Using in situ hybridization and receptor autoradiography, we were not able to detect clear signals of CRH1 receptor mRNA and CRH binding sites in the central amygdaloid nucleus of either group, confirming the reportedly low expression and density of CRH receptors in this brain area. The present data support the view that CRH receptors in the central nucleus of the amygdala are involved in the mediation and expression of anxiety-related behavior, but simultaneously raise questions as to the mechanisms of antisense oligodeoxynucleotide action.

Amygdala↗

PubMed1995

Anxiety: a potential predictor of vulnerability to the initiation of ethanol self-administration in rats.

Anxiolytic effects of ethanol have been proposed to be important factors in the initiation of ethanol consumption. To examine this hypothesis, drug-naive Wistar rats were tested in the elevated plus-maze to determine their initial level of anxiety. Based on their response, we separated the animals into anxious and non-anxious groups. After that, animals went through an oral ethanol self-administration procedure. Rats that were initially classified as anxious showed a significantly (P < 0.01) higher intake and preference for ethanol during the initiation phase of the voluntary drinking procedure than non-anxious animals. In another experiment, intraperitoneal (IP) injections of ethanol (0.5-1.5 g/kg) produced dose-dependent anxiolytic effects in rats when tested in the elevated plus-maze procedure. Blood ethanol levels following IP injections during the plus-maze test were similar to those reached during the oral ethanol self-administration procedure, which shows that the rats indeed drank sufficient amounts of ethanol to experience its anxiolytic effects. These findings indicate that the basal level of anxiety plays an important role in vulnerability to alcohol drinking.

Alcohol Drinking↗

PubMed1995

Long-term antidepressant treatment reduces behavioural deficits in transgenic mice with impaired glucocorticoid receptor function.

Impaired cognitive function and enhanced activity of the hypothalamic-pituitary-adrenocortical system are among the cardinal symptoms of major depression in humans that resolve after successful antidepressant treatment. We used a transgenic mouse model expressing antisense RNA complementary to that of glucocorticoid receptor (GR) mRNA to test the hypothesis that reduced GR function can cause these clinical disturbances. The transgenic mice show profound behavioural changes in a number of animal tests that are indicative of cognitive impairment. These mice also have elevated plasma corticotropin concentrations in response to stress. After long-term treatment with moclobemide, a reversible inhibitor of monoamine oxidase type A that acts clinically as an antidepressant, both the behavioural deficits and the hormonal alterations disappeared. These observations suggest that a transgenic mouse with GR dysfunction may be a useful model for investigation of drug effects on the cognitive and neuroendocrine aspects of depression.

Animals↗

PubMed1995

V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats.

To develop and validate a vasopressin (AVP) receptor knockdown strategy, we infused an antisense oligodeoxynucleotide to the V1 subtype mRNA into the septum of male rats with osmotic minipumps and measured behavioral, cellular and molecular parameters. Compared to vehicle and scrambled-sequence oligo controls, chronic antisense administration for up to 4 d diminished the ability of the animals to distinguish a previously exposed juvenile from a novel one and to respond to exogenous AVP (1 ng/5 microliters, intracerebroventricular) with an improved social memory. Furthermore, anxiety-related behavior was reduced. As measured in the behaviorally tested rats, antisense treatment resulted in a reduced binding of radiolabeled AVP in the septum, but not in other limbic brain areas (receptor autoradiography), and an increased amount of V1 receptor mRNA (reverse transcriptase PCR), indicating translational arrest and ongoing transcriptional activity. In sense oligo-treated rats, on the other hand, both the social and the anxiety-related behavior scores lay between levels obtained in control and antisense-treated animals. These sense-treated rats showed a slightly reduced V1 receptor density in the septum and reduced receptor mRNA levels, indicating hybridization of the sense oligo to the DNA. The data show the potential of antisense targeting to further reveal relationships between local gene expression, neuropeptide-receptor interactions in distinct brain areas, and behavioral performance.

Analysis of Variance↗

PubMed1994

Corticotropin-releasing hormone (CRH) antisense oligodeoxynucleotide treatment attenuates social defeat-induced anxiety in rats.

1. The neuropeptide corticotropin-releasing hormone (CRH) is the main mediator of the neuroendocrine and behavioral response to stress. End-capped phosphorothioate antisense and sense oligodeoxynucleotides (ODN) corresponding to the start coding region of rat CRH mRNA were infused intracerebroventricularly (30 micrograms/3 microliters per injection) three times at 12 hr intervals. Six hours after the last injection rats were subjected to social defeat stress and subsequently tested on the elevated plus maze. 2. Socially defeated CRH antisense-treated rats displayed markedly reduced anxiety-related behavior, as they spent significantly more time in the open arms of the plus maze compared to sense ODN- and vehicle-treated animals. 3. In controls, social defeat evoked a stress-induced elevation of CRH mRNA and CRH in the hypothalamus and a significant increase in plasma corticotropin (ACTH) levels. These parameters were attenuated in antisense-injected rats. 4. Our results suggest that CRH antisense treatment is effectively suppressing the neuroendocrine and behavioral effects of social defeat.

Agonistic Behavior↗