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Biomedical subjects

Conan Kornetsky

Publications and source records attributed to Conan Kornetsky.

8 recordsLinked to original sources
PubMed2006

Nociceptive threshold and analgesic response to morphine in aged and young adult rats as determined by thermal radiation and intracerebral electrical stimulation.

The present experiment compared the nociceptive threshold and analgesic response to morphine in young (4-5 months) and aged (24 months) rats using peripheral thermal stimulation and intracerebral electrical stimulation. Responses to thermal stimuli were assessed using both the classical tail-flick procedure in which latency of response is the dependent variable and a new method in which threshold in calories of heat is the dependent variable. In the intracerebral nociceptive threshold procedure, electrical stimuli were delivered via an electrode implanted in the mesencephalic reticular formation (MRF), a pain pathway, and the animals were trained to terminate the stimulation by turning a cylindrical manipulandum embedded in one wall of the experimental chamber. For the classical tail-flick method, the aged rats required a greater intensity of stimulation to produce a basal response latency that was between 2.5 and 3.5 s. Using the new psychophysical method for determining the tail-flick threshold, the aged rats' basal thresholds were significantly higher than that of the young rats. However, the basal thresholds obtained by direct stimulation of the MRF failed to show a significant age effect, suggesting that the registration of pain is not different between young and aged rats. These age-related differences in baseline tail-flick response may be due to changes in the spinal reflex associated with aging. Although, there was no difference in the analgesic effects of morphine between young and aged rats using the latency of the tail-flick response, evidence for decreased analgesic response was seen using the tail-flick threshold measure and the intracerebral stimulation threshold method.

Analgesics, Opioid↗
PubMed2004

Brain-stimulation reward, morphine-induced oral stereotypy, and sensitization: implications for abuse.

Early professionals believed that it was unlikely that anyone but the emotionally unstable received pleasure and became addicted to narcotic drugs. This position was well entrenched and influenced much of the thinking well into the latter half of the last century. Although the discovery of a brain reward system was made early in the 1950's it was not until 20 years later that this discovery was applied to the study of the mechanisms involved in the rewarding aspects of abused substances. Along this vein results will be shown in which opiate antagonist block the dopamine agonist activation of the brain reward system as well as the corollary. Sensitization of the reward system suggests that a driving force for drug use is 'liking' and not just 'wanting.' Basal changes in cerebral metabolic rates of glucose are seen in the presence of cues associated with morphine experience, giving evidence for the role of drug related cues in craving. Finally we asked the question 'Do old rats have as much fun as young rats?'

Animals↗
PubMed2004

The effects of cocaine on the rate independent brain stimulation reward threshold in the mouse.

Interest in the development of mouse models of drug abuse liability has increased with the introduction of selective gene expression. In the rat, the ability of drugs to lower brain stimulation reward (BSR) thresholds often correlates with high abuse liability. Measurement of BSR thresholds using rate-independent methods decreases the influence of impaired motor performance on threshold determination that may confound studies of mutant mice. In the present experiment, the effects of cocaine on mouse BSR thresholds were assessed using a modification of the rate-independent psychophysical method of limits as current intensity was systematically varied in a series of descending and ascending discrete trials. Bipolar electrodes were implanted into the medial forebrain bundle of male C57Bl/6N mice and the effects of intraperitoneal saline and cocaine (5.0-30.0 mg/kg) on BSR thresholds were assessed using a within-subject crossover design. Threshold was defined as the intensity at which the mouse would respond in 50% of the trials. Threshold levels were significantly lowered below levels of control following cocaine administration with the maximum lowering following a 20.0-mg/kg dose. These findings indicate that cocaine increases the sensitivity of the mouse to BSR, and that BSR thresholds can be determined using rate-independent methods in this species.

Animals↗
PubMed2004

Effects of morphine on brain-stimulation reward thresholds in young and aged rats.

Mesolimbic opioid systems are altered with aging; however, the effects of these changes on the rewarding actions of opioids have not been examined. The present experiment assessed differences in the responsiveness of brain reward pathways in young and aged rats to the effects of morphine using the brain-stimulation reward (BSR) model. Aged (24 months) and young (5 months) male F344/BNF1 rats were stereotaxically implanted with a bipolar stainless steel electrode into the lateral hypothalamic (LH) region of the medial forebrain bundle. Thresholds were determined using the rate-independent psychophysical method. Each animal was tested after the administration of saline or morphine at 0.5, 1, 2.5, 5 and 10 mg/kg doses. A significant difference in the mean baseline threshold between aged (99.8+/-6 microA) and young rats (149.1+/-14 microA) was observed. Although in both groups morphine lowered the BSR threshold, there were no significant differences between the groups except at the 10-mg/kg dose, the difference did approach significance. This study indicates that there are baseline differences in the rewarding threshold in the two groups, that morphine lowers the threshold in young and aged animals and that the hedonic effects produced by morphine, for the most, part remain preserved in aged animals.

Aging↗
PubMed2004

Increased sensitization to morphine-induced oral stereotypy in aged rats.

Sensitization develops to the stereotypic biting behavior that appears with the repeated administration of high dose morphine to rats. Because there is evidence that this behavior is dopamine-mediated and that there are age-related changes in dopamine systems, we compared the development and expression of morphine-induced biting behavior in aged (24 months) and young rats (5 months). Animals were treated with four sensitizing 10 mg/kg doses of morphine or saline, followed by three weekly challenges with 4 mg/kg doses of morphine or saline. By the fourth sensitizing morphine dose and after the administration of each low dose challenge, the biting time was significantly greater for aged than for young morphine pre-treated rats. After the first weekly low dose challenge, the aged but not young animals expressed more biting than when they did after the last 10 mg/kg dose. These results indicate that sensitization to morphine-induced oral stereotypy is significantly greater in aged as compared to young rats. Age-related enhanced sensitivity to morphine-induced oral stereotypy might be related to age-induced increases in vulnerability to opioid-induced insults to the basal ganglia, and may be a model for certain diseases of this pathway.

Aging↗
PubMed2002

Effects of cue exposure on brain glucose utilization 8 days after repeated cocaine administration.

Relapse to cocaine use may involve exposure to cocaine-associated environmental cues. The present experiment tested the hypothesis that basal local cerebral metabolic rate for glucose (LCMR(glu)), as measured by the 2-deoxy-D-[l-(14)C]glucose (2-DG) autoradiography, would change in the presence of cocaine conditioned cues at 8 days after the last of seven daily cocaine injections (30 mg/kg). This dose regimen results in sensitization to the locomotor effects of cocaine. Cocaine was administered to two groups of rats while saline was administered to a third. In the conditioned group, the rats were placed into the 2-DG experimental chamber immediately after cocaine injection. Rats in the non-conditioned group were placed into their home cage after cocaine administration. A control group received only saline. The 2-DG experiment was conducted in non-drugged animals 8 days after treatment completion. The interaction between treatment status and brain region was significant. Mean basal LCMR(glu) was significantly lower in 12 brain regions in the conditioned group as compared to the control group, but was significantly lower in only four areas in the non-conditioned group. Regions in which there were significant changes in the conditioned group included the basolateral amygdala, subiculum, medial thalamus, lateral habenula and the substantia nigra pars compacta. LCMR(glu) was significantly reduced in the ventrolateral orbital cortex and rostral nucleus accumbens in both experimental groups. These findings indicate that repeated cocaine administration can cause protracted decreases in basal LCMR(glu), decreases that are more widespread in the brain during exposure to cocaine-associated cues.

Animals↗
PubMed1988

Potentiation of morphine analgesia by D-amphetamine is mediated by norepinephrine and not dopamine.

Morphine will raise the threshold for escape from aversive electrical stimulation delivered to the mesencephalic reticular formation and this effect is potentiated by D-amphetamine. In order to study the roles which dopamine and norepinephrine play in modulating opiate analgesia, the effects of amfonelic acid, an indirect dopamine agonist, and nisoxetine, a selective norepinephrine reuptake blocker, were determined alone and in combination with morphine using this supraspinal model of analgesia. Amfonelic acid alone produced hyperalgesia and completely antagonized the analgesic effect of morphine. Nisoxetine had no effect by itself, however, it potentiated the analgesic effect of morphine when the two drugs were administered concomitantly. These findings suggest that norepinephrine and not dopamine plays a predominant role in the potentiation of opiate analgesia by D-amphetamine.

Amphetamine↗