Biomedical subjects

C Jodogne

Publications and source records attributed to C Jodogne.

7 recordsLinked to original sources

PubMed1994

Inhibition of corticosterone synthesis by Metyrapone decreases cocaine-induced locomotion and relapse of cocaine self-administration.

Several studies have recently shown that basal and stress-induced secretion of corticosterone may enhance vulnerability to drugs of abuse. In this report, we studied the effects of metyrapone, an inhibitor of the synthesis of corticosterone, on cocaine-induced locomotion and on the relapse of cocaine self-administration. Locomotor response to cocaine was studied because psychomotor effects of drugs have been shown to be related to their reinforcing properties. Self-administration was studied in the relapse phase since blockade of relapse is central to the therapy of addiction. Before these behavioral tests, rats in different experimental groups were injected subcutaneously with either metyrapone (100 mg/kg) or vehicle, twice a day for 8 days. Metyrapone treatment reduced cocaine-induced locomotor activity and relapse of cocaine self-administration, without inducing a nonspecific disruption of motor or food-directed behaviors. Under these experimental conditions, the metyrapone treatment totally blocked stress-induced corticosterone secretion but did not modify basal corticosterone levels. These results confirm the involvement of glucocorticoids in the pathophysiological mechanisms underlying vulnerability to drug abuse, and may have implications for the development of new therapeutic strategies of drug addiction.

Analysis of Variance↗

PubMed1994

Animals predisposed to develop amphetamine self-administration show higher susceptibility to develop contextual conditioning of both amphetamine-induced hyperlocomotion and sensitization.

It has been shown that rats, like humans, display individual differences in the propensity to develop psychostimulant self-administration. Animals showing the highest locomotor reactivity to novelty (HRs: High Responders) are more prone to develop amphetamine self-administration than rats having a low locomotor response to novelty (LRs: Low Responders). The present study was designed to ascertain whether individual differences are also present in the conditioning of drug effects, a process involved in the maintenance of addiction. After pairing the drug effect with a particular set of environmental cues, only HRs showed conditioned hyperlocomotion and environment-specific sensitization to the effect of amphetamine. Unconditioned sensitization was, however, observed in LRs but not in HRs. The environment-specific sensitization disappeared on extinction of the conditioned hyperlocomotion in HRs, indicating that conditioning facilitates the expression of sensitization. In contrast, an inhibitory influence of conditioning on sensitization emerged from the analysis of the same results over all the experimental groups, without taking individual differences into account. In conclusion, our results show that: (i) locomotor reactivity to novelty predicts both vulnerability to develop self-administration and contextual conditioning of drug effects, which suggests that the two phenomena are two related features and that conditioning plays an important role not only in the maintenance of drug intake but also in its development; (ii) conditioned and unconditioned sensitization can be developed separately in different individuals which suggests that they are independent phenomena; (iii) analysis of individual differences is relevant to pharmacological studies, especially with respect to drugs of abuse.

Amphetamine↗

PubMed1993

Behavioral sensitization and tolerance to the D2 agonist RU 24213: dissociation between several behavior patterns in mice.

Previous studies have shown that different components of behavioral effects of indirect agonists given chronically to laboratory rodents can follow different courses during treatment. Whether repeated injections of a D2 agonist can lead to the same phenomenon was investigated in mice using the D2 agonist N-n-propyl-N-phenylethyl-p-(3-hydroxy-phenyl)-ethylamine (RU 24213). Five mutually exclusive behaviors were examined over seven intermittent administrations (every other day over 13 daily injections) of RU 24213 (2.5 mg/kg SC) in mice. Rapid tolerance to the clearest initial effect of RU 24213, stillness, was found. Suppression of grooming also showed tolerance later in the treatment regimen (from the fourth test). From the third test, parallel time courses of sensitization were obtained for ambulation and rearing. Sleeping position was strongly depressed throughout the chronic treatment. These results show that the development in time of the behavioral effects of RU 24213 injected chronically strongly depend upon the behavioral measure. This supports the use of multiple measures in the same animal in the behavioral analysis of chronically injected dopaminergic drugs.

Animals↗

PubMed1992

Oxytocin blocks the environmentally conditioned compensatory response present after tolerance to ethanol-induced hypothermia in mice.

The present study tested the hypothesis that the attenuation by oxytocin of tolerance to ethanol-induced hypothermia relies upon an impairment of the putative conditioning processes underlying environment-specific tolerance. According to the conditioning model of tolerance, such tolerance occurs because an opposite compensatory response conditioned to ethanol-paired cues attenuates ethanol's effects. Tolerance to ethanol-induced hypothermia was established to a particular environment over 4 days by injecting mice (daily) with oxytocin 2 h before ethanol, outside the colony room. As controls, other mice were injected similarly but following testing in the animal room. We found that oxytocin suppressed the conditioned compensatory response, revealed by injecting saline to every group in the tolerance-associated environment. These results suggest that oxytocin acted, at least partly, via an inhibition of the associative learning processes that facilitate tolerance development.

Animals↗

PubMed1991

Adult-like biphasic neurobehavioral changes induced by a GABA-A agonist in infant and weanling mice.

The neurobehavioral responsivity to peripherally injected muscimol, a gamma-aminobutyric acid-A (GABA-A) agonist, was assessed in infant (14-day-old), weanling (20-day-old) and young adult (53-day-old) outbred male mice. In the first experiment, relatively high doses of muscimol (ranging from 0.05 to 0.40 mg/kg in developing and from 0.50 to 3 mg/kg in adult animals) were found to dose-dependently induced solid catalepsy and ataxia, evaluated 5 times at 20-min intervals. In the second experiment, the GABA agonist was injected in dose ranges which include relatively small concentrations in order to assess its excitatory properties, observable in adults, on rearing and locomotion in developing mice. It appeared that levels of rearing and especially locomotion were enhanced at the low doses (0.025 and 0.050 mg/kg in developing, and 1.3 and 1.9 mg/kg in adult mice) and inhibited at the higher ones (0.150 mg/kg in developing and 1.9 and 2.5 mg/kg in adult mice). This adult-like biphasic action of muscimol in developing mice--excitation at low and depression/sedation at high doses--strongly suggests a full maturation of the GABA-A-related behavioral functions at a period of ontogeny where adult-like locomotion emerges. Given that previous studies have shown that muscimol can biphasically affect behavioral activity in newborn murines as well, it is suggested that GABA-related behavioral functions mature near-monotonically during ontogeny, unlike those related to other major neurotransmitter systems.

Aging↗

PubMed1991

Oxytocin attenuates tolerance not only to the hypothermic but also to the myorelaxant and akinesic effects of ethanol in mice.

Inhibition of ethanol tolerance by oxytocin has been demonstrated previously using the hypothermic effect only. The purpose of the present experiment was to investigate the effect of oxytocin on the development of tolerance to ethanol-induced hypothermia, myorelaxation and akinesia in mice. Four groups of mice received daily intraperitoneal injections of saline or oxytocin (0.005 mg) plus saline or ethanol (2 g/kg). The peptide was administered 2 hours before ethanol. For five consecutive days, temperature measurements were performed 20 minutes before and after ethanol injection. Myorelaxation and akinesia were evaluated following the second temperature measure. Oxytocin pretreatment, which had no intrinsic effects, resulted in a robust selective attenuation of tolerance to ethanol-induced hypothermia, myorelaxation and akinesia. These results suggest that the mechanisms for peptide modulation are common to these three typical effects of ethanol.

Animals↗

PubMed1990

Modulation of tolerance to the GABAA agonist THIP by environmental cues.

The present experiment assessed the extent to which environmental stimulation could influence tolerance to the sedative and catatonic effects of the GABAA agonist, 4,5,6,7-tetrahydroisoxozolo(5,4-c)pyridin-3-ol (THIP), through associative learning processes. A conditioning paradigm was used, with THIP as unconditioned stimulus and environmental cues as conditioned stimulus. One group of mice received 15 mg/kg THIP in the testing environment; the second group was exposed to THIP in the colony room, while a third group received only saline. On a tolerance testing session, all mice received 15 mg/kg THIP in the testing environment. Results show that mice previously given THIP in the testing environment display a greater tolerance than mice receiving the drug in the alternative environment. Subsequently, a placebo was given to all mice in the testing environment to assess the influence of environmental cues alone; mice previously given THIP in the testing environment exhibited an enhancement of motility. The results agree with an associative model of tolerance which predicts that environmental cues associated with drug exposure elicit a conditioned compensatory response that cancels the unconditioned effect of the drug.

Animals↗