Biomedical subjects

Cynthia L Kenmuir

Publications and source records attributed to Cynthia L Kenmuir.

6 recordsLinked to original sources

PubMed2006

Acetaminophen self-administered in the drinking water increases the pain threshold of rats (Rattus norvegicus).

Previous studies have suggested that the addition of flavored acetaminophen suspension (for example, Children's Tylenol) in the drinking water of rats may not be effective in producing postoperative analgesia because of low levels of consumption. However, these investigations neither measured analgesia nor compared the consumption by rats that had undergone surgery with that by unmanipulated rats. The present study reports that although unmanipulated rats naive to the taste of flavored acetaminophen do indeed drink significantly less of this liquid than tap water, they drank sufficient amounts of the acetaminophen-containing solution to significantly raise pain thresholds, as measured by the hot-plate test. Moreover, rats that had undergone surgery drank significantly more acetaminophen solution than did those that had no surgery. These data suggest that oral self-administration of flavored acetaminophen by rats may be an appropriate means to reduce pain.

Acetaminophen↗

PubMed2005

A role for prefrontal cortex in the extinction of a conditioned taste aversion.

This study used immunohistochemical methods to determine if the medial prefrontal cortex (mPFC) is involved in the extinction of a conditioned taste aversion (CTA). As rats reached 90% reacceptance of a tastant (saccharin: SAC) that had previously been associated with lithium chloride-induced malaise, c-Fos protein expression increased dramatically as compared to animals with active CTAs, animals without CTAs (i.e., explicitly unpaired CS-US exposures) or animals drinking SAC for the first time. These data indicate a role for mPFC (prelimbic and infralimbic cortex) in the formation of a CTA extinction memory.

Animals↗

PubMed2004

Long-term age-dependent behavioral changes following a single episode of fetal N-methyl-D-Aspartate (NMDA) receptor blockade.

BACKGROUND: Administration of the N-methyl-D-aspartate (NMDA) antagonist ketamine during the perinatal period can produce a variety of behavioral and neuroanatomical changes. Our laboratory has reported reliable changes in learning and memory following a single dose of ketamine administered late in gestation. However, the nature of the drug-induced changes depends on the point during embryonic development when ketamine is administered. Embryonic day 18 (E18) rat fetuses pre-treated with ketamine (100 mg/kg, i.p. through the maternal circulation) and taught a conditioned taste aversion (CTA) learn and remember the CTA, whereas E19 fetuses do not. The current study sought to determine if long-term behavioral effects could be detected in animals that received ketamine or a saline control injection on either E18 or E19. Rat behavior was evaluated on two different measures: spontaneous locomotion and water maze learning. Measurements were collected during 2 periods: Juvenile test period [pre-pubertal locomotor test: Postnatal Day 11 (P11); pre-pubertal water maze test: P18] or Young-adult test period [post-pubertal locomotor test: P60; post-pubertal water maze test: P81]. RESULTS: Water maze performance of ketamine-treated rats was similar to that of controls when tested on P18. Likewise, the age of the animal at the time of ketamine/saline treatment did not influence learning of the maze. However, the young-adult water maze test (P81) revealed reliable benefits of prenatal ketamine exposure - especially during the initial re-training trial. On the first trial of the young adult test, rats treated with ketamine on E18 reached the hidden platform faster than any other group - including rats treated with ketamine on E19. Swim speeds of experimental and control rats were not significantly different. Spontaneous horizontal locomotion measured during juvenile testing indicated that ketamine-treated rats were less active than controls. However, later in development, rats treated with ketamine on E18 were more active than rats that received the drug on E19. CONCLUSION: These data suggest that both the day in fetal development when ketamine is administered and the timing of post-natal behavioral testing interact to influence behavioral outcomes. The data also indicate that the paradoxical age-dependent effects of early ketamine treatment on learning, previously described in fetuses and neonates, may also be detected later in young adult rats.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

Dynamic processing of taste aversion extinction in the brain.

While substantial advances have been made in discovering how the brain learns and remembers, less is known about how the brain discards information, reorganizes information, or both. These topics are not only relevant to normal brain functioning but also speak to pathologies in which painful memories do not wane but are evoked time and again (e.g., post-traumatic stress disorder; PTSD). Here, we measured brain activity (as indicated by the regional expression of c-Fos protein) in rats during acquisition and throughout extinction of a conditioned taste aversion (CTA). We compared that brain activity with animals that had intact CTA memories or those that experienced an explicitly unpaired (EU) conditioned stimulus (CS; saccharin, SAC) and unconditioned stimulus (US; lithium chloride, LiCl). The data show a dynamic and nonuniform pattern of c-Fos protein expression in brain nuclei known to mediate gustation and CTAs. In particular, brainstem nuclei (e.g., nucleus of the solitary tract; NTS) and the basolateral nucleus of the amygdala (BLA) are active early as CTAs are formed and as extinction of the learned response begins. Later in the extinction process, the BLA reduces c-Fos expression relative to nonextinguished controls. Finally, as almost full reacceptance of the taste is achieved, the gustatory neocortex (GNC) expresses enhanced levels of c-Fos protein. Thus, extinction of a CTA is not represented by a simple reversal of the c-Fos activity evoked by CTA conditioning. Rather, the data demonstrate that extinction of conditioned responses is a dynamic process in which the activity levels of particular nuclei along the brain's taste pathway change depending on the extent to which the conditioned response has been extinguished.

Analysis of Variance↗

PubMed2004

Repeated exposures to gustatory stimuli produce habituation or positive contrast effects in perinatal rats.

Adult rats exhibit a decrease in consummatory responses following repeated presentations of a taste (habituation) and an increase in consummatory responses if they experience an upward shift in the magnitude or intensity of a gustatory stimulus (e.g., sucrose or saccharin). These responses do not represent a direct sensorimotor reaction to a gustatory cue, but rather reflect a change in responding based on the memory of a previous taste. Here, we sought to determine if fetal rats could (like adults) adjust their orofacial motor responses based on a memory of recent gustatory experience. Embryonic Day 18 (E18) or Day 19 (E19) rat fetuses received oral lavage with either 0.15 or 0.30% saccharin (SAC). Subsequently, observations of orofacial movements (mouthing and licking) following oral lavage with 0.30% SAC were made 50 min later, 24 hr later, or on postnatal Day 3 (P3). Thus, some animals were in a "shifted" condition in which they first experienced a relatively low concentration of SAC and then a higher one while control rats ("nonshifted") received 0.30% SAC during both taste exposures. Fetuses exhibited evidence of both habituation (with repeated presentation of the 0.30% SAC) and positive contrast effects (PCEs) (following an upward shift in SAC concentration) when retested 50 min after their first exposure to SAC on E19. However, these animals did not exhibit PCEs 24 hr later or 5 days later (on P3). Contrast effects were not observed when the initial SAC exposure was on E18, and habituation responses were variable depending on the time interval between the taste presentations to these animals. Rats with a 5- to 6-day latency between the two taste presentations showed neither PCEs nor habituation. Our data indicate that PCEs and habituation effects emerge at different ages, and their demonstration is dependent upon the latency between the taste presentations.

Animals↗

PubMed2002

Simple behavioral methods to assess the effect of drugs or toxins on sensory experience.

When behavioral pharmacologists/toxicologists study conditioned taste aversions (CTAs), or other conditioned responses, as a means to investigate the effects of various drugs or toxins on a learned response, failure to discover a CTA is frequently attributed to the treatment's influence on the associative process. This kind of analysis may fail to identify drug-induced sensory changes that may influence conditioned stimulus (CS) or unconditioned stimulus (US) saliency. The current paper outlines a simple method by which a drug's influence on CS or US sensation may be determined. Further, illustrative data are provided regarding how N-methyl-D-aspartate (NMDA) receptor blockade modulates taste and the sensation of malaise. Ketamine (an NMDA receptor antagonist) has been reported to block CTAs in both neonatal and adult rats. The current experiments evaluated ketamine's ability to modulate the taste of a frequently employed CS (saccharin HCl=SAC) or the aversive aspects of a common US (Lithium Chloride=LiCl). Rats normally exhibit a preference for 0.3% SAC over 0.6% SAC and will suppress consumption of these liquids following an injection of LiCl. We report that ketamine did not markedly antagonize these consummatory patterns nor did it disrupt spontaneous locomotor movements. Taken together, these findings point to ketamine's limited ability to change the sensory capacities required for CTA formation. Investigators interested in determining the underlying causes of drug-induced CTA blockade may choose to employ paradigms similar to the one used here.

Animals↗