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Biomedical subjects

I Lucki

Publications and source records attributed to I Lucki.

At least 91 records · Page 5Linked to original sources
PubMed1989

Behavioral effects of 8-OH-DPAT: studies using the Microtaxic ventricular injector.

This study introduces the Microtaxic Ventricular Injector, a plastic mold that allows for the rapid administration of drugs into the ventricular system of adult rats. The Microtaxic Ventricular Injector was used to destroy serotonin (5-HT) neurons by administering the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 100 micrograms/10 microliters) into the lateral cerebroventricles. Injection of the 5-HT neurotoxin produced a 79% depletion of 5-HT in the cortex and an 86% depletion of 5-HT in the hippocampus. In addition, 5,7-DHT treatment produced a two-fold shift to the left of the dose-response curve of the 5-HT1A agonists 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT) or 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in producing the 5-HT syndrome indicating the development of denervation supersensitivity following the destruction of 5-HT neurons. In addition, the behavioral effects of 8-OH-DPAT were studied when administered to different CNS sites using the Microtaxic Ventricular Injector. 8-OH-DPAT (10 micrograms) injected into the fourth ventricle produced the 5-HT syndrome in 100% of the rats tested within a 3 min time period. In contrast, 8-OH-DPAT injected into the lateral ventricle produced the syndrome in only 33% of the rats tested and with a 6-9 min delay until this effect occurred. These results indicate the greater potency of 8-OH-DPAT at producing the 5-HT syndrome when administered in ventricular sites that are close to its locus of action in the brainstem/spinal cord region. These experiments demonstrate the usefulness and reliability of the Microtaxic Ventricular Injector as an instrument for rapidly injecting drugs directly into different cerebroventricular sites.

5,7-Dihydroxytryptamine↗
PubMed1989

Effect of 1-(m-chlorophenyl)piperazine and 1-(m-trifluoromethylphenyl)piperazine on locomotor activity.

The piperazine-type 5-hydroxytryptamine (5-HT) agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP), 1-(m-chlorophenyl)-piperazine (m-CPP), 1-(p-chlorophenyl)piperazine (p-CPP) and MK-212 [6-chloro-2-(1-piperazinyl)pyrazine], produced a dose-dependent suppression of spontaneous ambulatory behavior in rats. Pretreatment with the 5-HT antagonists metergoline, methysergide or mianserin, but not selective 5-HT2 or catecholamine antagonists, blocked the reduction of activity caused by TFMPP suggesting that the stimulation of 5-HT receptors was involved in causing this behavioral effect. Other behavioral signs of 5-HT receptor stimulation, such as the 5-HT behavioral syndrome or head-shaking behavior, were not observed in rats injected with TFMPP, m-CPP or MK-212 except at toxic doses. The ability of piperazine agonists to reduce locomotor activity in rats was altered by long-term changes in 5-HT neurotransmission. The destruction of 5-HT neurons by i.v.t. injection of the neurotoxin 5,7-dihydroxytryptamine potentiated the ability of m-CPP to inhibit ambulatory behavior. On the other hand, elevating 5-HT content by administering the monoamine oxidase inhibitors phenelzine or nialamide for 7 days reduced the ability of m-CPP to suppress locomotor activity. Acute administration of the monoamine oxidase inhibitors, or chronic administration of other antidepressants such as desmethylimipramine or iprindole, failed to alter m-CPPs activity-suppressant effects. These studies suggest that chronic changes in 5-HT neurotransmission produce compensatory changes which alter the behavioral response to these piperazine agonists. Taken together with other evidence that both TFMPP and m-CPP are agonists at 5-HT1B and 5-HT1C receptors, the effects of TFMPP and m-CPP on locomotor activity may be associated with the selective activation of 5-HT1C, or possibly 5-HT1B, receptors.

Animals↗
PubMed1988

Effects of intrabulbar injections of 6-hydroxydopamine on ethyl acetate odor detection in castrate and non-castrate male rats.

The function of norepinephrine-containing neurons which project to the olfactory bulb is poorly understood. Although there has been suggestion that norepinephrine (NE) may modulate general olfactory sensitivity by attenuating the inhibitory feedback of granule cells upon mitral and tufted cells, behavioral indices of olfactory sensitivity have not been measured in animals with depletions of bulbar NE. The present experiment used computerized olfactometry and signal detection methodology to assess the odor detection performance of castrate and non-castrate male rats to a range of perithreshold concentrations of ethyl acetate following 6-hydroxydopamine (6-OHDA) depletion of bulbar NE. Such depletion had no significant influence on odor detection performance at any of the odorant concentrations examined in either castrate or non-castrate animals, as indexed by the non-parametric sensitivity measure SI. This observation implies that general olfactory sensitivity is unaltered by major depletion of intrabulbar NE, but does not preclude the possibility that NE modulates sensitivity to select odorants or odorant mixtures, or alters detection ability under atypical states of arousal.

Acetates↗
PubMed1988

The effect of anxiolytic drugs on memory in anxious subjects.

The benzodiazepines (BZs), represented by diazepam, are the class of drugs used most frequently to treat clinical anxiety disorders. Since it is known that acute BZ intake impairs memory function, the effects of BZs on memory were evaluated in chronic users of BZ medications. In addition, the acute effects of diazepam were compared with those of the non-BZ anxiolytic buspirone on memory function in anxious subjects. Memory function was evaluated by a free verbal recall procedure where subjects recalled a list of 16 noncategorized nouns immediately after the word list was read (immediate recall) and again 20 min later (delayed recall). When the chronic BZ users were tested for free verbal recall during their first visit, 4-14 h after their last dose, they did not differ in immediate or delayed recall from an age- and sex-matched group of unmedicated anxious subjects. At a subsequent visit, the acute effects of BZ medications were studied 60-90 min after the subjects took their usual dose. Although acute BZ administration did not alter immediate recall, delayed recall was significantly impaired in the chronic BZ users. Thus, complete tolerance does not develop to the acute memory-impairing effects of BZs after long-term use. Acute administration of the anxiolytic drugs diazepam (5 mg) or buspirone (5 or 10 mg) did not alter immediate recall in another group of unmedicated anxious subjects. Diazepam selectively impaired delayed recall of the word list when compared with placebo. In contrast, neither dose of buspirone altered delayed recall. To the extent that such effects on verbal recall tests are reflected in a patient's daily activities, the failure of buspirone to adversely affect memory function could contribute to its usefulness as an alternative antianxiety therapy.

Adult↗
PubMed1988

Reduction of feeding behavior by the serotonin uptake inhibitor sertraline.

Administration of the selective serotonin (5-HT) uptake inhibitor sertraline produced a dose-dependent reduction of food intake in rats. Doses of sertraline of 10 mg/kg or greater reduced the intake of solid pellets significantly (P less than 0.01) during the 1st hour of a 4-h feeding test in rats deprived of food and water for 24 h. Food intake during the remaining 3 h and water intake during the feeding test was unaffected by sertraline. Sertraline (2-18 mg/kg IP) also reduced milk consumption in food-deprived rats. Pretreatment with the nonselective 5-HT antagonists metergoline (2 mg/kg IP) or methysergide (3.3 mg/kg IP) blocked sertraline's inhibition of dry food intake, whereas pretreatment with the selective 5-HT2 receptor antagonist ketanserin (3.3 mg/kg IP) or the peripheral 5-HT2 antagonist xylamidine (2.5 mg/kg IP) failed to block sertraline's anorexic effect. The feeding-suppressant effect of 10 mg/kg sertraline was prevented following the destruction of central 5-HT neurons by the 5-HT neurotoxic agent, 5,7-dihydroxytryptamine (200 micrograms ICV). This result is consistent with sertraline's anorexic effect depending on intact 5-HT neurotransmission. Therefore, sertraline appears to reduce feeding by enhancing the action of endogenous serotonin at central synapses mediated by 5-HT1 rather than 5-HT2 receptors.

1-Naphthylamine↗
PubMed1988

Rapid discrimination of the stimulus properties of 5-hydroxytryptamine agonists using conditioned taste aversion.

Separate groups of rats were trained to discriminate the stimulus properties of selective agonists at 5-HT receptors using a conditioned taste aversion procedure. Fluid-restricted rats were injected with drug or saline and then given access to a 0.25% saccharin solution for 30 min. When rats received a drug trial, saccharin consumption was followed by an injection of LiCl (1.8 mEq/kg i.p.), whereas on saline trials saccharin consumption was followed by a second injection of saline instead of LiCl. Rats were trained using injections of either 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.), an agonist selective for the 5-HT1A receptor, or 1-(m-trifluoromethylphenyl)piperazine (0.8 mg/kg i.p.), an agonist selective for 5-HT1B and 5-HT1C receptors, as the drug stimuli. Acquisition of the discriminated taste aversion, as measured by the differential effects on saccharin drinking between drug and saline trials, required only two to three pairings of either drug stimulus with LiCl injections. The 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus cue generalized to other drugs that are selective for the 5-HT1A receptor, such as ipsapirone (8-16 mg/kg i.p.) or buspirone (4 mg/kg i.p.), but not to agonists that are selective for the 5-HT1B/1C receptor, such as 1-(m-trifluoromethylphenyl)piperazine or 1-(m-chlorophenyl)piperazine. The discriminative stimulus properties of 1-(m-trifluoromethylphenyl)piperazine generalized to 1-(m-chlorophenyl)piperazine (0.2-0.8 mg/kg i.p.) but not to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (0.4 mg/kg i.p.).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Serotonin-induced head shaking behavior in rats does not involve receptors located in the frontal cortex.

Serotonin-induced head shaking behavior, a response associated with 5-HT2 receptors, was examined in rats with lesions of the frontal cortex because of the high density of 5-HT2 receptors in this area. Head shaking behavior caused by the serotonin precursor, 5-hydroxy-L-tryptophan, or by the serotonergic agonist, quipazine, was unchanged following the complete ablation of the frontal cortex. Although 5-HT2 receptors are associated with the head shake response, this behavior is probably not related to serotonin receptors located in the frontal cortex.

5-Hydroxytryptophan↗
PubMed1987

The role of the aural head shake reflex in serotonin-mediated head shaking behavior.

The head shake reflex is a rapid rhythmic shaking of the head in a radial motion and is a prominent part of the behavior of most mammalian species. The administration of agonists at 5-hydroxytryptamine (5-HT) receptors to rats increases apparently-spontaneous head shaking behavior. The present study examined the relationship between the head shake reflex, elicited by stimulation of the aural ampullae with Tween 80, with a similar-appearing behavior, the head shake response caused by the administration of 5-HT agonists to rats. Head shaking was attenuated by the subcutaneous infiltration of the local anesthetic procaine into the posterior border of the external auditory meatus. However, the local anesthetic did not alter head shake behavior produced by administering either the 5-HT agonist quipazine or the 5-HT precursor 5-hydroxy-L-tryptophan (L-5-HTP). The magnitude of the head shake reflex was also diminished after habituation of the reflex by repeatedly applying Tween 80 to the ampullae, yet this treatment had no effect on the head shaking behavior caused by quipazine. In a complementary manner, pretreatment with the 5-HT2 receptor antagonist ketanserin potently blocked shaking behavior caused by quipazine without significantly altering the head shake reflex. Chronic administration of the atypical antidepressant drug iprindole to rats for 7 days reduced quipazine-induced shaking behavior without affecting the head shake reflex. In contrast, chronic administration of the monoamine oxidase inhibitor phenelzine to rats for 7 days reduced head shaking behavior caused by either stimulus, indicating that an attenuation of motor reflex activity could play a role in the reduced response to quipazine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Long-term effects of yohimbine on behavioral sensitivity to a stressor.

Two experiments examined the long-term effects of repeated administration of yohimbine, a suspected anxiogenic drug, on behavioral sensitivity to a conditioned cue for shock. In Experiment 1, rats were trained to bar press following injection of yohimbine (either 1 or 2 mg/kg) or saline. At the end of this training, injections were suspended and the rats were given Pavlovian fear conditioning to establish a light as a shock signal. Rats were then returned to the bar press situation (about 2 weeks after their last injection) and the capacity of the light to disrupt responding was tested. Rats previously treated with yohimbine were less disrupted by the light than were controls. In contrast, Experiment 2 found that previously experiencing the yohimbine-induced state only in the home cage increased subsequent disruption of bar pressing by the light. Yohimbine pretreatment had no effect on acquisition of freezing behavior to the light, nor on bar pressing during testing in the absence of the light, in either experiment. The results show that yohimbine can have long-term effects on behavior in the presence of a stressor, and that the nature of these effects are dependent upon environmental and/or behavioral context in which the yohimbine-induced state was experienced. These findings appear compatible with an internal stimulus view of stress and stress inoculation.

Animals↗
PubMed1987

The long-term effects of diazepam and pentylenetetrazol on behavioral sensitivity to a stressor.

Rats were trained to bar press for sucrose reinforcement following daily injections of 20 mg/kg pentylenetetrazol (PTZ), 5 mg/kg diazepam (DZ), or saline. At the end of 12 days of this training, all injections were suspended for the remainder of the experiment. Five days later, the rats were given 10 days of Pavlovian fear conditioning (two trials per day) to establish a light as a shock signal. Next, the rats were returned to the bar press situation to test the capacity of the light to suppress responding. Rats previously treated with DZ showed stronger conditioned fear of the light than did rats originally trained following injections of either PTZ or saline. In contrast, bar pressing by PTZ-treated rats was less suppressed by light than was control performance. The results indicate that modification of the behavioral effects of environmental stressors can be a long-term consequence of drug treatments. DZ treatments had the long-term effect of increasing behavioral disruption by a stressor, while treatment with PTZ reduced the stressor's negative behavioral impact. These findings appear compatible with the idea that behavioral sensitivity to stressors is dependent, in part, on learning about the stimulus properties of internal states.

Animals↗
PubMed1987

Differential effects of the anxiolytic drugs, diazepam and buspirone, on memory function.

The effects of the anxiolytic drugs diazepam (5 mg) or buspirone (5 or 10 mg) were studied in comparison with placebo on memory function in 39 subjects diagnosed with generalized anxiety disorder. Neither drug altered the immediate recall of a list of 16 nouns or impaired digit span, a second test of immediate memory. Diazepam selectively impaired the recall of nouns after a 20 min delay when compared with placebo. In contrast, neither dose of buspirone altered the delayed recall of the word list. The implications of such different effects of anxiolytic drugs on memory function for the clinical treatment of anxiety are discussed.

Anti-Anxiety Agents↗
PubMed1986

Chronic use of benzodiazepines and psychomotor and cognitive test performance.

The performance of 43 long-term users (average = 5 years) of benzodiazepine (BZ) medications was examined on a battery of behavioral tasks, cognitive tests, and subjective mood rating scales. The performance of the chronic BZ users did not differ significantly from age- and sex-matched anxious subjects, except that critical flicker fusion (CFF) thresholds were lower and subjective ratings of tranquilization were higher in the BZ users. Twenty-two subjects were reexamined in order to determine the acute effects of BZ medications in long-term users. The acute administration of BZ medications significantly increased CFF thresholds, improved digit-symbol substitution test performance, impaired the delayed recall of verbal material, increased subjective ratings of tranquilization, and reduced physical sedation. Motor performance tests were not impaired and subjective feelings of sedation were not increased after the acute administration of BZs by chronic users. During withdrawal from long-term BZ use (17 subjects), CFF thresholds were elevated, subjective ratings of physical sedation and anxiety were increased, but performance on other psychomotor and cognitive tests was not altered. The results suggest that tolerance develops selectively to different behavioral and subjective effects of BZ medications with their continued use. Tolerance failed to develop to the antianxiety effects, the reduction of CFF threshold, and to the impairment of short-term memory caused by BZs. However, chronic users of BZ medications failed to demonstrate psychomotor-impairing or sedating effects to BZ medications. The results have implications for evaluating the safety of the long-term use of BZ medications.

Adult↗
PubMed1986

Hormonal and behavioral effects associated with intravenous L-tryptophan administration.

Doses of 5.0, 7.5 and 10.0 g L-tryptophan, the amino acid precursor of serotonin, or saline alone were administered by IV infusion to a group of 11 healthy male subjects, and both hormonal and behavioral responses were monitored. Significant increases were observed in plasma concentrations of growth hormone and prolactin after all three doses of L-tryptophan, but not after saline infusion. No alterations in cortisol or thryotropin were noted at any level. Examination of behavioral effects of L-tryptophan revealed a dose-dependent impairment in performance on the symbol copying test. In addition, L-tryptophan produced significant effects on mental and physical sedation, but did not alter subjective ratings of tranquilization. In agreement with some prior reports, these observations support the ability of L-tryptophan, when administered IV in high doses, to produce pronounced effects on the central nervous system in humans, and suggest the potential utility of this paradigm as a neuroendocrine challenge test.

Adult↗