Biomedical subjects

Kevin B Freeman

Publications and source records attributed to Kevin B Freeman.

6 recordsLinked to original sources

PubMed2005

Assessment of monoamine transporter inhibition in the mediation of cocaine-induced conditioned taste aversion.

Although the mechanisms of cocaine reward have been well characterized, the pharmacological basis of cocaine's aversive effects is less understood. Using the conditioned taste aversion (CTA) preparation, the present study examined the role of monoamine uptake inhibition in cocaine's aversive effects by comparing cocaine to three reuptake inhibitors with relative specificity for the transporters of dopamine (DAT; GBR 12909), norepinephrine (NET; desipramine) and serotonin (SERT; clomipramine). Specifically, 104 male Sprague-Dawley rats were given 20-min access to a novel saccharin solution followed immediately by a subcutaneous injection of cocaine, GBR 12909, desipramine, clomipramine (each at 18, 32 or 50 mg/kg; 12 groups) or drug vehicle (equivolume to the highest cocaine dose). Over trials, cocaine and desipramine each dose-dependently suppressed saccharin consumption and did so in an equivalent manner when matched by dose. However, both GBR 12909 and clomipramine conditioned weaker aversions than cocaine at the two lowest doses (18 and 32 mg/kg). At the highest dose (50 mg/kg), GBR 12909 produced equivalent suppression of saccharin consumption to cocaine while clomipramine's conditioned suppression remained relatively weak at this dose. These results suggest that cocaine's adrenergic actions resulting from NET inhibition may play a more significant role in the mediation of its aversive effects than its actions at DAT and SERT.

Analysis of Variance↗

PubMed2005

The interaction of sex and route of drug administration in cocaine-induced conditioned taste aversions.

Although taste aversion learning has been reported to be a function of a variety of factors, one that has received considerable attention is the subject's sex, wherein males generally display stronger taste aversions than females. An exception to these findings is with cocaine for which females have been shown to display greater aversions than males. Although suggestive of a Sex x Drug interaction, cocaine was administered subcutaneously (s.c.) in this report while others administered drug intraperitoneally (i.p.). Thus, there may be a Sex x Route interaction. To address the contributions of sex and route in cocaine aversions, the present study examined aversions in male and female Sprague-Dawley rats administered a range of doses of cocaine either s.c. or i.p. At the two higher doses of cocaine tested (20 and 32 mg/kg), aversions were a function of route with animals injected s.c. with cocaine displaying greater aversions than those injected i.p. Although there was no main effect of sex at either dose there was an interaction between sex and route at the 20 mg/kg dose. Specifically, s.c.-injected males displayed stronger aversions than i.p.-injected males. There were no differences between the two routes for females. Further, males displayed stronger aversions than females when injected s.c. There was no sex difference when both groups were injected i.p. This interaction was no longer evident at the highest does of cocaine (32 mg/kg). These data indicate that sex differences in aversion learning with cocaine are a function of the route of cocaine administration (and are dose specific).

Animals↗

PubMed2004

Assessment of the contributions of Na+ channel inhibition and general peripheral action in cocaine-induced conditioned taste aversion.

While the rewarding properties of cocaine appear to be mediated by its blockade of central monoamine uptake, the mechanisms and sites of action for cocaine's aversive effects have yet to be determined. Using the conditioned taste aversion (CTA) preparation, the present study examined the role of Na(+) channel blockade in cocaine's aversive effects by comparing cocaine to the local anesthetic procaine at three doses (18, 32 and 50 mg/kg). Furthermore, the role of cocaine's peripheral actions in its aversive effects was examined by comparing cocaine to the quaternary analog cocaine methiodide (equimolar to the three doses of cocaine) in establishing CTAs. Procaine and cocaine methiodide each dose-dependently suppressed saccharin consumption, indicating that the aversive effects of cocaine are, in part, mediated by its inhibition of Na(+) channels and via its activity in the PNS. However, the fact that the aversions induced by procaine and cocaine methiodide were weaker than those induced by cocaine at each dose tested suggests other factors are involved in its aversive effects. Possible reasons for the weaker aversions induced by procaine and cocaine methiodide relative to cocaine were discussed.

Animals↗

PubMed2004

Conditioned taste aversion: a database.

The present commentary describes the availability of a database on conditioned taste aversion learning, the avoidance of fluids and foods previously associated with the aversive effects of a variety of drugs. The database includes articles as early as 1955 by Garcia and his colleagues [Science 122 (1955) 127] (reporting such avoidance in rats) and papers just published given that the database is ongoing and constantly updated. At the printing of this announcement, approximately 2600 papers are included in the database. The database allows the user to search for articles by author(s), key word(s), date, title and journal. These terms can be used as single entries or multiple combinations. Finally, the full database can be viewed by performing the search function without entering any terms in the query window. The database can be accessed at http://www.CTALearning.com.

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↗

PubMed2002

Autologous chondrocyte repair of an articular defect in the humeral head.

Articular cartilage lesions remain a difficult problem for the patient and physician. A variety of procedures and treatments have been proposed to lessen symptoms and restore the articular surface. The knee joint has been the focus of the vast majority of these cartilage restoration procedures. Articular cartilage lesions of the humerus are significantly less common, and their management remains poorly defined. This paper presents a case report of a young athlete with a large full-thickness articular cartilage defect of the proximal humerus and subsequent treatment using autologous chondrocyte implantation.

Adolescent↗