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R Stefanski

Publications and source records attributed to R Stefanski.

At least 19 recordsLinked to original sources
PubMed2004

Effects of morphine on gene expression in the rat amygdala.

Influence of morphine self-administration on gene expression in the rat amygdala was studied using rat genome DNA arrays U34A from Affymetrix. Animals were trained to self-administer morphine, each having two 'yoked' control animals, receiving passive injections of either morphine or saline. After 40 sessions of self-administration, amygdalae were removed, total RNA was isolated and used to prepare probes for Genechip arrays. The treatment was found to significantly change abundance of 29 transcripts. Analysis by means of reverse transcription real-time PCR showed significant changes in abundance of five transcripts: gamma protein kinase C (PKC), upstream binding factor 2 (UBF2), lysozyme, noggin and heat shock protein 70 (hsp70). After 30 days of forced abstinence from morphine self-administration, abundance of hsp70 and lysozyme returned to basal levels. Changes in abundance of UBF2 persisted, and abundance of three additional genes, namely nuclear factor I/A, gamma1 subunit of GABAA receptor and the neuronal calcium sensor 1, changed. Additionally, acute as well as chronic intraperitoneal morphine administration changed the abundance of PKC gamma, gamma1 subunit of GABAA and hsp70 genes.

Amygdala↗
PubMed2000

Clinical impact of second harmonic imaging and left heart contrast in echocardiographic stress testing.

Second harmonic imaging and left heart contrast agents are recent echocardiographic advancements that enhance the assessment of wall motion. Because little information exists concerning their clinical impact on echocardiographic stress testing in daily practice, this was determined for 9-month periods before (1997) and after (1998) their introduction. Harmonic imaging was used in all patients after its introduction. A second generation intravenous left heart contrast agent (Optison) was used at the discretion of the sonographer and physician team. Both exercise and dobutamine stress tests were included. At the time of study interpretation, diagnostic confidence was assigned as high, medium, or low. For all patients who underwent coronary angiography < or = 6 months after stress testing, the diagnostic accuracy was determined (true positive plus true negative/total studies). There were 574 studies before and 746 studies after implementation. Optison was used in 28% of the harmonic imaging studies. Study cancellations due to uninterpretable images fell from 6.4% to 1.2% (p <0.001) despite a more obese population completing testing (body mass index: 29 +/- 7 to 31 +/- 8 kg/m2, p = 0.02), whereas high diagnostic confidence increased from 55% to 64% (p <0.001). For the 7% of patients who underwent cardiac catheterization, the diagnostic accuracy remained unchanged (74 vs 73%) although a prior negative stress test was less common (40% to 20% p = 0.04). Thus, these new technologies had a favorable clinical impact.

Albumins↗
PubMed1999

Neuroadaptations in the dopaminergic system after active self-administration but not after passive administration of methamphetamine.

Methamphetamine is a strong and long-lasting stimulant that can be easily synthesized and is effective when taken either orally, intravenously, or smoked as 'ice'. Due to it's escalating abuse, a clear need exists for laboratory procedures to evaluate motivational components of methamphetamine abuse and their underlying neurobiological mechanisms. In the present experiment, we utilized a 'yoked' procedure in which rats were run simultaneously in groups of three, with two rats serving as yoked controls which received an injection of either 0.1 mg/kg methamphetamine or saline which was not contingent on responding each time a response-contingent injection of 0.1 mg/kg methamphetamine was self-administered by the third paired rat. Rats that had actively self-administered methamphetamine for 5 weeks and were then withdrawn from methamphetamine for 24 h showed marked decreases in somatodendritic dopamine D2 autoreceptors levels in the ventral tegmental area (34%) and medial (31%) and dorsal (21%) part of the substantia nigra zona compacta with a corresponding down-regulation of dopamine D1 receptors in the shell of the nucleus accumbens (15%), as measured by in vitro quantitative autoradiography. Since the decreases in levels of dopamine D1 and D2 receptors which occurred in rats self-administering methamphetamine did not occur in littermates that received either yoked injections of methamphetamine or saline, these changes likely reflect motivational states that were present when methamphetamine injection depended on active drug self-administration behavior.

Animals↗
PubMed1998

Studies on the role of nicotinic acetylcholine receptors in the discriminative and aversive stimulus properties of ethanol in the rat.

The role of the nicotinic acetylcholine receptor (nAChR) in the discriminative and aversive stimulus effects of ethanol was studied in rats. In the operant drug discrimination procedure the rats were trained to discriminate between 1.0 g/kg ethanol and saline under the FR10 schedule of sweetened milk reinforcement. Neither the nAChR agonist, nicotine (0.1-0.6 mg/kg) nor the nAChR antagonist, mecamylamine (3.0-6.0 mg/kg) substituted for the ethanol stimulus. Moreover, mecamylamine (0.5-6.0 mg/kg) did not antagonise the ethanol stimulus. The cross-familiarisation conditioned taste aversion procedure was used as an alternative method to study stimulus resemblance between ethanol and nicotine. Six daily injections of nicotine (0.6 mg/kg) significantly decreased a subsequent ethanol-induced taste aversion conditioning. The aversive stimulus effects of ethanol were investigated with the conditioned taste aversion (CTA) paradigm. Mecamylamine (1.0-3.0 mg/kg) did not attenuate an ethanol-induced CTA. These results suggest that: (1) nAChRs are not primarily involved in the discriminative stimulus effects of ethanol when studied with the operant drug discrimination test; (2) nAChRs are not critically involved in the ethanol-induced CTA.

Animals↗
PubMed1998

5-HT1A receptor agonist (8-OH-DPAT) and 5-HT2 receptor agonist (DOI) disrupt the non-cognitive performance of rats in a working memory task.

The present study investigated the role of 5 -HT1A and 5 -HT2 receptors in the execution of a working memory task (delayed non-matching to position, DNMTP) by assessing the influence of 8-OH-DPAT (5-HT1A receptor agonist) and DOI (5-HT2 receptor agonist) on the performance of rats lesioned with 5,7-dihydroxytryptamine (5,7-DHT) and their controls. Post-mortem neurochemical analysis revealed that serotonin and 5-hydroxyindoleacetic acid levels were reduced in examined brain areas (especially in the hippocampus where there was a 90 percent reduction). Noradrenaline concentrations were also decreased (mostly on the same side of the injection) by about 20 percent. 5,7-DHT lesioned rats did not significantly differ from their controls in performance in the DNMTP task. At the 30 microg/kg dose, 8-OH-DPAT did not affect the DNMTP-performance of rats, but at the higher dose (100 microg/kg) it reduced the probability of responding to the sample lever. DOI (100 and 300 microg/kg) also interfered with the non-cognitive performance of rats. Since neither of these agonists affected significantly the choice accuracy, they do not appear to influence the working memory per se. The 5,7-DHT lesioned rats did not differ from their controls in response to these agonists. These results suggest that the combination of 5-HT1A receptor stimulation by 8-OH-DPAT and 5-HT2 receptor stimulation by DOI can interfere with the non-cognitive performance of rats in the DNMTP task. The results further indicate that the effect of 8-OH-DPAT may be mediated through post-synaptic rather than pre-synaptic 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Discriminative stimulus properties of ethanol in the rat: differential effects of selective and nonselective benzodiazepine receptor agonists.

Rats were trained to discriminate between ethanol (1.0 g/kg; 10% v/v) and saline under a fixed ratio 10 schedule of sweetened milk reinforcement. Both diazepam [nonselective, full benzodiazepine (BZ) receptors agonist] and bretazenil (nonselective, partial BZ receptor agonist) produced dose-dependent ethanol-appropriate responding (>75%). Neither diazepam nor bretazenil affected the response rate at the doses producing maximal generalisation from ethanol. In contrast, zolpidem (full BZ1 receptor agonist) and abecarnil (full BZ1/full or partial BZ2 receptor agonist) produced only moderate (<50%) ethanol-appropriate responding when tested up to doses that markedly decreased the overall response rate. These results suggest that: 1) there are no major differences between full and partial, nonselective BZ receptor agonists in their ability to substitute for 1.0 g/kg dose of ethanol; 2) stimulation of BZ1 receptors alone is not sufficient to produce ethanol-like discriminative stimulus effects in the rat.

Animals↗
PubMed1996

Competitive NMDA receptor antagonist, CGP 40116, substitutes for the discriminative stimulus effects of ethanol.

A drug discrimination procedure was used to compare the ability of competitive (CGP 37849, D,L-(E)-2-amino-4-methyl-5-phosphono-3-pentanoate; CGP 40116, D-(E)-2-amino-4-methyl-5-phosphono-3-pentanoate) and non-competitive (dizocilpine) NMDA receptor antagonists to substitute for ethanol in rats trained to discriminate between a 1.0 g/kg dose of ethanol (i.p.) and saline. Dizocilpine (0.1-0.3 mg/kg) substituted partially for ethanol at doses that markedly reduced the rate of responding. CGP 37849 (1.25-5.0 mg/kg) substituted partially for ethanol and suppressed the response rate. CGP 40116 (0.5-2.5 mg/kg), and active D-stereoisomer of CGP 37849, completely substituted (88%) for ethanol, and caused only moderate suppression of the response rate.

2-Amino-5-phosphonovalerate↗
PubMed1996

Metrifonate improves spatial navigation and avoidance behavior in scopolamine-treated, medial septum-lesioned and aged rats.

We investigated the effects of acute p.o. pretraining treatment with an indirect acetylcholinesterase inhibitor, metrifonate, on water maze spatial navigation and passive avoidance behavior. Metrifonate (10-100 mg/kg, orally, p.o.) did not improve the water maze or passive avoidance performance of young intact rats. However, in young rats metrifonate over a broad dosage range (10-100 mg/kg, p.o.) was able to alleviate the adverse effects of scopolamine (a muscarinic acetylcholine receptor antagonist; 0.4 and 2.0 mg/kg in water maze and passive avoidance study, respectively) and medial septum-lesioning on spatial reference and working memory and passive avoidance performance. In old (23-month-old) rats, a defect of water maze and passive avoidance behavior was observed. In old rats, metrifonate improved spatial reference memory function in the water maze and also passive avoidance at 10-30 mg/kg, but the 3 mg/kg dose was ineffective. Very old (27-month-old) rats had a more severe impairment of water maze performance than old rats, and metrifonate 3-30 mg/kg did not improve their spatial navigation. These results show that metrifonate may over a wide range of doses stimulate cognitive functioning, but during advanced aging neurobiological defects develop that may mask some of the therapeutic effects of metrifonate in rats.

Aging↗
PubMed1996

Studies on the role of 5-HT3 receptors in the mediation of the ethanol interoceptive cue.

The drug discrimination test was used to evaluate the role of 5-HT3 receptors in the mediation of the stimulus properties of ethanol in rats trained to discriminate between ethanol (1.0 g/kg, 10% v/v, i.p.) and saline vehicle. Rats trained to discriminate between a lower dose of ethanol (0.5 g/kg i.p.) failed to attain discrimination criteria after 20 weeks (100 sessions) of training. None of the doses of 5-HT3 receptor antagonists (0.001, 0.01, 0.1, 1.0, 10.0 mg/kg of tropisetron or ondansetron) administered i.p. 30 min before ethanol, antagonized the discriminative stimulus properties of ethanol. Furthermore, none of the centrally (1, 10, 35 micrograms per rat) or i.p. (0.1, 1.0, 2.5, 5.0, 10.0 mg/kg) administered doses of 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide, could replace the ethanol discriminative cue. These results suggest that 5-HT3 receptors are not primarily involved in the mediation of the stimulus properties of ethanol.

Animals↗
PubMed1996

Effects of combined block of alpha 1-adrenoceptors and NMDA receptors on spatial and passive avoidance behavior in rats.

The present study was designed to investigate the interactions between alpha 1-adrenoceptors and NMDA receptors in modulating spatial navigation and passive avoidance behavior in rats. Pretraining treatment with prazosin, and alpha 1-adrenoceptor antagonist, at 2 mg/kg i.p., impaired acquisition performance in a water maze navigation test and had no effect on passive avoidance behavior. Posttraining and pretest injections of prazosin had no effect on water maze or passive avoidance behavior. Pretraining treatment with ((+/-))-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive NMDA receptor antagonist, does dependently (3 and 10 mg/kg) impaired passive avoidance and water maze behavior. Posttraining treatment with CPP had no effect on water maze and passive avoidance behavior. A pretraining combination of subthreshold doses of CPP (1 mg/kg) and prazosin (1 mg/kg) impaired water maze behavior. A combination of subthreshold doses of CPP (3 mg/kg) and prazosin (1 mg/kg) injected posttraining or pretest had no marked effect on water maze or passive avoidance performance. A control experiment showed that CPP 3 mg/kg or CPP 1 mg/kg and prazosin 1 mg/kg injected pretraining had no effect on cue navigation to a clearly visible platform, but CPP 10 mg/kg markedly impaired performance. The present results indicate that alpha 1-adrenoceptors and NMDA receptors may synergistically regulate acquisition of spatial navigation performance. Therefore, it would be interesting to study the effects of combined stimulation of alpha 1-adrenoceptors and NMDA receptors on age-related memory defects.

Adrenergic alpha-Antagonists↗
PubMed1994

Antidepressant treatment and limbic serotonergic mechanisms regulating rat locomotor activity.

The effects of chronic administration of desipramine, citalopram, and electroconvulsive shocks (ECS) on changes in rat motility after intraaccumbens (NAS) injections of selective serotonergic drugs were studied in intact and 5.7-DHT lesioned animals. It was shown that local injections of 8-OHDPAT and DOI-HCl depressed rat locomotor activity. Their effects appeared to be mediated postsynaptically, and could be antagonized by NAN-190 and ritanserin, respectively. Chronic but not acute pretreatment of rats with antidepressants (21 days long; the experiment was performed 24 h after the last dose) as well as repeated ECS (shocks were applied five times every second day), antagonized behavioral depression after 8-OHDPAT and DOI-HCl. The influence of antidepressant treatment was prevented by serotonergic lesions. Chronic administration of antidepressants and ECS did not equivocally affect the levels or metabolism of 5-HT, dopamine, and noradrenaline in the rat limbic forebrain. It is concluded that the present data indicate diminished activity of 5-HT systems related to the 5-HT1A and 5-HT2 receptors in the limbic nucleus, after chronic antidepressant treatment. This effect of drugs and ECS concerns nervous processes linked with the function of postsynaptically localized 5-HT receptor subtypes, and it probably depends on intact presynaptic 5-HT innervation.

5,7-Dihydroxytryptamine↗
PubMed1989

Interaction between accumbens D1 and D2 receptors regulating rat locomotor activity.

The effect of intra-accumbens injections of various dopaminergic agonists and antagonists on the rat locomotor activity has been evaluated in automated open fields. Locomotor stimulation has been observed after local administration of d-amphetamine (10 micrograms), apomorphine (10 micrograms), as well as of solution containing the D1 agonist SKF 38 393 and D2 receptor agonist LY 171 555 (quinpirole) in doses (10 and 4 micrograms, respectively) which were inactive when both drugs were administered separately. On the other hand separate injections of metoclopramide (0.1 microgram) and SCH 23 390 (0.5 microgram) (D2 and D1 receptor antagonists) very potently inhibited animals' locomotor activity. The data indicate that concomitant stimulation of both accumbens D1- and D2-receptor related mechanisms is a necessary condition to increase rat motility. Moreover, it seems that accumbens D1 receptors may be differently involved in the control of facilitatory versus inhibitory motor processes.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗