Biomedical subjects

Kenneth J Sufka

Publications and source records attributed to Kenneth J Sufka.

13 recordsLinked to original sources

PubMed2006

Antinociceptive profile of salvinorin A, a structurally unique kappa opioid receptor agonist.

Salvinorin A, is a structurally unique, non-nitrogenous, kappa opioid receptor (KOP) agonist. Given the role of KOPs in analgesic processes, we set out to determine whether salvinorin A has antinociceptive activity in thermal and chemo-nociceptive assays. The tail-flick assay was employed to investigate 1) salvinorin A's (0.5, 1.0, 2.0, and 4.0 mg/kg) dose-response and time-course (10, 20, and 30 min) effects in a thermal nociceptive assay, and 2) the ability for the KOP antagonist norBNI (10.0 mg/kg) to prevent salvinorin A antinociception. The hotplate assay was utilized as a second thermal nociceptive measure to test salvinorin A's dose-response effects. The acetic acid abdominal constriction assay was used to study salvinorin A's dose-response and time-course (over 30 min) effects in a chemo-nociceptive assay. Together, these studies revealed that salvinorin A produces a dose-dependent antinociception that peaked at 10 min post-injection but rapidly returned to baseline. Additionally, pretreatment with the KOP antagonist norbinaltorphimine (norBNI) reversed salvinorin A-induced antinociception. These findings demonstrate that salvinorin A produces a KOP mediated antinociceptive effect with a short duration of action.

Acetic Acid↗

PubMed2006

Modeling anxiety-like states: pharmacological characterization of the chick separation stress paradigm.

While previous research has sought to validate the chick separation stress paradigm as an anxiolytic screening assay, it is unknown whether the paradigm better models a nonspecific anxiety-like state or something similar to panic disorder or generalized anxiety disorder. To characterize the anxiety model pharmacologically, cockerels were administered drug probes that were either: (1) only effective for treating panic disorder (phenelzine 3.125-25.0 mg/kg), (2) effective for treating both panic disorder and generalized anxiety disorder (alprazolam 0.065-0.5 mg/kg; clonidine 0.1-0.25 mg/kg; imipramine 1.0-15.0 mg/kg), (3) only effective for treating generalized anxiety disorder (buspirone 2.5-10.0 mg/kg; trazodone 0.1-3.0 mg/kg) or (4) capable of exacerbating symptoms of panic disorder in humans (yohimbine 0.1-3.0 mg/kg). At 7 days after hatch, chicks received either vehicle or drug probe intramuscularly 15 min prior to social separation under a mirror (low-stress) or no-mirror (high-stress) condition for a 180-s observation period. Dependent measures were distress vocalizations to index separation stress and sleep-onset latency to index sedation. Phenelzine, alprazolam, imipramine and clonidine were able to attenuate distress vocalizations (at doses without significant sedation) whereas buspirone and trazodone did not. Paradoxically, yohimbine modestly attenuated distress vocalizations. These results suggest that the chick separation stress paradigm better models panic disorder than generalized anxiety disorder as an anxiolytic screen.

Animals↗

PubMed2006

Modeling the anxiety-depression continuum hypothesis in domestic fowl chicks.

Anxiety and depression are currently classified as separate clinical syndromes despite considerable similarities in their symptoms, pathophysiological substrates and response to treatment interventions. An alternative hypothesis views anxiety and depression along a temporal continuum, a construct that the current research attempts to model in a preclinical setting. In experiment 1, socially raised domestic fowl chicks separated from conspecifics demonstrated a pattern of distress vocalizations that sequentially models anxiety-like and depressive-like states. In addition, administration of the benzodiazepine anxiolytic chlordiazepoxide and the tricyclic antidepressant imipramine provided pharmacological validation for the model in that they were capable of dissociating the anxiety-like and depressive-like states. In experiment 2, corticosterone levels were quantified across the isolation test session to provide convergent validity to the model. These findings fit well with the human clinical literature on the anxiety-depression continuum perspective, and suggest the consideration of a nosology that emphasizes the inter-relatedness of these clinical states rather than their boundaries.

Animals↗

PubMed2005

Screening antidepressants in the chick separation-stress paradigm.

RATIONALE: Clinical research has indicated that antidepressants are efficacious in the treatment of anxiety disorders, especially when repeatedly administered. However, few animal models of anxiety are sensitive to antidepressants, a finding that may be due to procedures limited to acute administrations. OBJECTIVES: The purpose of the present research was to further validate the chick separation-stress paradigm as an animal model of anxiety by examining its sensitivity to the monoamine oxidase inhibitor (MAOI) phenelzine (6.25, 12.5, 25.0 mg/kg), the tricyclic antidepressant (TCA) imipramine (5.0, 10.0, 20.0 mg/kg), the selective serotonin reuptake inhibitor (SSRI) citalopram (1.0, 2.5, 5.0 mg/kg), and the norepinephrine reuptake inhibitor (NRI) maprotiline (5.0, 10.0, 20.0 mg/kg) under acute (no pretreatment) or repeated (3 or 6 days pretreatment) administration procedures. METHODS: Following any pretreatment, 8-day-old chicks received their respective vehicle or drug probe injection 15 min before tests in either a "mirror" (low stress) or "no mirror" (high stress) condition for a 180-s isolation period. The dependent measures were distress vocalizations to index separation stress and sleep onset latency to index sedation. RESULTS: The model was sensitive to acutely administered phenelzine (MAOI), imipramine (TCA), and maprotiline (NRI), but not citalopram (SSRI) and retained its sensitivity to these drug probes across both repeated administration procedures. None of the drug probes possessed any sedative properties. CONCLUSIONS: These results help extend the validity and utility of the chick separation-stress paradigm as an animal model of anxiety by demonstrating its sensitivity to antidepressants under both acute and repeated administration procedures.

Animals↗

PubMed2005

Opioid receptor function in social attachment in young domestic fowl.

Opioid systems are implicated in social attachment processes. This research sought to determine the functional contribution of each opioid receptor in modulating social attachment/separation distress. Following ICV administration of opiate probes, 7-day-old cockerels were isolated from conspecifics for a 3 min test period under either a mirror or no-mirror condition. Vocalizations served as the measure of separation-stress. Opioid receptor probes included: the mu agonist DAMGO (0.02, 0.19, 1.95 nmol), the mu antagonist CTOP (0.009, 0.09, 0.9 nmol), the delta agonist SNC80 (0.3, 1.0, 3.0 micromol), the delta antagonist naltrindole (0.2, 2.2, 22.2 nmol), the kappa agonist U50, 488 (1, 30, 100 nmol), the kappa antagonist norBNI (1.3, 13.6, 136.1 nmol), the NOP agonist N/OFQ (0.01, 0.1, 1.0 nmol), and the NOP antagonist UFP-101 (0.1, 1.0, 10.0 nmol). DAMGO attenuated separation distress vocalizations. No other drug probe enhanced or attenuated distress vocalizations. Further, the non-selective opiate antagonist naloxone (0.3, 8.3, 27.5 nmol) did not exacerbate distress vocalizations. These results suggest that only the mu receptor modulates social attachment in young domestic fowl.

Analgesics, Opioid↗

PubMed2004

The chick separation stress paradigm: a validation study.

To expand the generalizability of the chick separation stress paradigm as a high-throughput anxiolytic screen, six positive drug probes (doses in mg/kg: meprobamate 15-120, pentobarbital 2.5-20.0, chlordiazepoxide 2.5-15.0, buspirone 2.5-10.0, imipramine 1-15, and clonidine 0.10-0.25) and five negative drug probes (amphetamine 0.5-4.0, scopolamine 0.2-1.6, caffeine 5-20, chlorpromazine 1-30, and haloperidol 0.03-1.00) were evaluated in the test. Seven-day-old chicks received intramuscular injections of either vehicle or drug probe 15 min prior to tests in either a mirror (low-stress) or a no-mirror (high-stress) condition for a 3-min observation period. The dependent measures were distress vocalizations to index separation stress and sleep onset latency to index sedation. All positive drug probes attenuated distress vocalizations in a dose-dependent manner, except buspirone. All positive drug probes affected sleep onset latency in a dose-dependent manner, except buspirone and imipramine. In all cases, the anxiolytic-like effect of positive drug probes was greater than its sedative effect. None of the negative drug probes affected either distress vocalizations or sleep onset latency, except for the highest dose of amphetamine, which caused pronounced stereotypy. These findings demonstrate that this anxiolytic screen is sensitive to a wide range of positive pharmacological probes and insensitive to a wide range of negative pharmacological probes.

Animals↗

PubMed2004

High-performance liquid chromatographic determination of xanthohumol in rat plasma, urine, and fecal samples.

Xanthohumol (XN) is the major prenylated flavonoid in hop plants and as such a constituent of beer. Pharmacological studies have shown that XN possesses marked antioxidant and antiproliferative effects. In order to study the resorption and metabolism of this compound, reversed-phase high-performance liquid chromatography is used for the determination of XN in rat plasma, urine, and feces. In session one, rats receive either oral or intravenous (iv) administration (20 mg/kg body weight) of XN. In session two, rats receive oral administration of 50, 100, 200, 400, and 500 mg/kg body weight XN for bioavailability studies at various dose levels. Plasma, urine, and feces are collected at varying time points and assayed for their XN content. Plasma levels of XN fell rapidly within 60 min after iv administration; no XN is detected in plasma after oral administration in either session. XN and its metabolites are excreted mainly in feces within 24 h of administration. The method is a reliable tool for performing studies of XN in different biological material.

Animals↗

PubMed2003

Characterization of the chick carrageenan response.

The present study characterized carrageenan inflammatory nociception in the 7-day-old domestic chick. The time course effects of foot withdrawal latency to a thermal stimulus and edema were examined over a 6-h period following an intraplantar carrageenan (0.0-1.0%) injection. Carrageenan-induced hyperalgesia and edema had a similar course of action, enduring for approximately 6 h, with a peak effect at approximately 2 h post carrageenan injection. Carrageenan inflammation was produced in a robust concentration dependent manner. Carrageenan hyperalgesia was induced at all concentrations tested and no carrageenan concentration effects were discerned. In a subsequent series of experiments we challenged the carrageenan inflammation model with systemic administration of the opioid agonist morphine, the nonsteroidal anti-inflammatory drug naproxen or the steroidal antiinflammatory drug dexamethasone. Morphine produced a dose dependent attenuation of carrageenan hyperalgesia but had no effect upon carrageenan inflammation. Naproxen produced a moderate attenuation of carrageenan inflammation and hyperalgesia. Dexamethasone dramatically attenuated both carrageenan hyperalgesia and inflammation. Collectively, these experiments characterize the chick carrageenan response and demonstrate the potential of the chick carrageenan inflammation model as a less expensive adjunct model of inflammatory nociception.

Analgesics, Opioid↗

PubMed2003

Anxiolytic properties of Piper methysticum extract samples and fractions in the chick social-separation-stress procedure.

Piper methysticum extract (Kava kava) possesses anxiolytic properties. However, it is unknown whether these effects are best predicted by total kavalactone content or by one or more of its primary kavalactone constituents. Using the chick social separation-stress procedure as an anxiolytic bioassay, P. methysticum samples containing 12.8-100.0% total kavalactones (Exp. 1) and fractions containing 1-6 kavalactones of varying concentrations (0.1-67.5%; Exps. 2-3) were screened for activity and compared against a 5.0 mg/kg dose of chlordiazepoxide (CDP; Exp. 3). Eight-day-old chicks received IP injections of either vehicle or test compounds 30 min before being placed in the presence of two conspecifics or in isolation for a 3 min observation period. Dependent measures were ventral recumbency latency (sedation), distress vocalizations, and a measure of stress-induced analgesia (in Exps. 1 and 2 only). P. methysticum extract samples attenuated distress vocalizations in a concentration-dependent manner. The P. methysticum fraction that contained the highest concentration of dihydrokavain attenuated distress vocalizations in a manner equivalent to that of CDP. The extract samples and fractions that possessed anxiolytic properties did not possess the sedative properties found in CDP. Collectively, these findings suggest that dihydrokavain may be necessary and sufficient in mediating the anxiolytic properties of P. methysticum extract.

Animals↗

PubMed2003

Corticosterone response in the chick separation-stress paradigm.

Corticosterone response to separation stress and its sensitivity to the anxiolytic, chlordiazepoxide (CDP), were examined in 7-day-old domestic fowl (Gallus gallus). Saline or CDP (8.0 mg/kg) was injected intramuscularly 30 min before tests. Chicks were placed in isolation either with or without mirrors for a 15-min observation period, in which distress vocalizations were recorded. After testing, chicks were euthanized and blood was collected for the corticosterone assay. Chicks tested in the No-Mirror condition displayed an increase in vocalizations that was attenuated by CDP. Similarly, corticosterone levels were highest in chicks tested in the No-Mirror condition; however, CDP only modestly attenuated corticosterone levels. The present findings demonstrate that corticosterone levels parallel the behavioral marker of distress vocalizations in this paradigm, but this biological marker may be less sensitive than the behavioral marker to benzodiazepine anxiolytic manipulations.

Animals↗

PubMed2002

Dissociation of stress behaviors in the chick social-separation-stress procedure.

Separation from conspecifics in chicks produces an increase in distress vocalizations and a decrease in response to a noxious stimulus (stress-induced analgesia). This study questioned the relative contributions of novelty to the test chamber and social separation in mediating these stress responses. Eight-day-old chicks were tested either in isolation or in the presence of two social companions for a 3-min observation period in which distress vocalizations were recorded as well as the frequency of footlifts in response to a 50-microl injection of 0.10% formalin into the plantar surface of the footpad. In Expt. 1, chicks received six, 3-min test chamber habituation trials (vs. no habituation) one per day before testing; in Expt. 2, chicks were tested with mirrors placed in the chambers (vs. no mirrors). In both studies, isolated chicks in control groups (i.e., no habituation or no mirror) exhibited increased distress vocalizations and decreased nociceptive responses. In Expt. 1, habituation to the test chamber attenuated stress-induced analgesia but did not affect distress vocalizations. In Expt. 2, placement of mirrors in the test chamber attenuated distress vocalizations but did not affect stress-induced analgesia. These findings demonstrate a dissociation of stress behaviors in the chick social-separation-stress procedure: the stress-induced analgesia response is primarily mediated by novelty to the test apparatus while the distress vocalizations response is mediated by separation from conspecifics.

Analysis of Variance↗

PubMed1996

Stimulus properties and antinociceptive effects of selective bradykinin B1 and B2 receptor antagonists in rats.

Research has documented the differential role of bradykinin (BK) B1 and B2 receptors in the mediation of inflammatory nociception and this research suggests that selective B1 antagonists may have therapeutic potential against chronic inflammatory pain. The present study sought to further define the stimulus properties (reinforcing and aversive effects) of the selective B1 antagonist des-Arg9,(Leu8)-BK (0.0, 0.03, 0.1, and 0.3 mg/kg) and the selective B2 antagonist HOE 140 (0.0, 0.1, 0.5, and 1.0 mumol/kg) in the Freund's adjuvant (100 microliters, i.p.) model of chronic inflammatory nociception using the place preference paradigm. In addition, this research examined the differential antinociceptive effects of these antagonists on the formalin test (2.5%). Des-Arg9,(Leu8)-BK exhibited antinociceptive effects against both the first and second phases of the formalin response; HOE 140 tended to increase nociceptive responding on both phases of the formalin response. In the place preference paradigm, des-Arg9,(Leu8)-BK, but not HOE 140, exhibited negatively reinforcing effects (i.e. analgesia) in adjuvant-inflamed animals and aversive effects in noninflamed control animals. Neither compound exhibited positively reinforcing effects (i.e. abuse potential). These results further define the stimulus properties of these selective BK antagonists and provide additional evidence to support the notion that B1 antagonists may possess therapeutic potential for conditions of chronic inflammatory pain.

Animals↗

PubMed1994

Conditioned place preference paradigm: a novel approach for analgesic drug assessment against chronic pain.

In response to concerns over the clinical relevance of analgesic testing paradigms which involve acute nociceptive stimuli, the present research examined the utility of the conditioned place preference (CPP) paradigm as a novel approach for determination of analgesic drug efficacy against chronic nociception. Rats display preferences for environments that have been previously paired with positively reinforcing drugs; whether place preference to the negatively reinforcing effects of analgesic drugs in an animal model of chronic pain occurs is yet unknown. The present research sought to determine whether animals experiencing chronic pain would display a place preference for an environment paired with analgesic drug treatment. Persistent inflammatory nociception was induced by unilateral injections of complete Freund's adjuvant (0.1 ml) into the rat hind paw. Place preference to the opiate agonist morphine, the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the non-steroidal anti-inflammatory drug (NSAID) indomethacin was examined in 3 separate experiments. Rats received 8 counter-balanced conditioning trials (4 drug, 4 no-drug) of 60 min each with various drug doses (morphine: 3.0 and 10.0 mg/kg; indomethacin: 2.5 and 5.0 mg/kg; MK-801: 0.03, 0.1 and 0.3 mg/kg, i.p.) or vehicle serving as the reinforcing stimuli in a 3 compartment (2 stimuli, 1 neutral) place preference apparatus. In general, morphine place preference was observed in both inflamed and non-inflamed groups; inflamed groups exhibited enhanced morphine place preference than non-inflamed groups. MK-801 produced a low-dose place preference in inflamed animals; higher doses of MK-801 produced a place aversion in both inflamed and non-inflamed groups. Indomethacin failed to produced place preference in either inflamed or non-inflamed groups. These data demonstrate that the negatively reinforcing properties of analgesic drugs can be assessed via the CPP paradigm. In addition, this paradigm offers greater clinical relevance as animals determine drug efficacy without the involvement of high-intensity, phasic nociceptive stimulation.

Analgesics↗