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Antoine Coquerel

Publications and source records attributed to Antoine Coquerel.

8 recordsLinked to original sources
PubMed2006

Interactions of buprenorphine and dipotassium clorazepate on anxiety and memory functions in the mouse.

Buprenorphine, a partial mu-receptor agonist widely substituted for heroin in the treatment of addiction, is often misused in combination with benzodiazepines. Improved hedonic properties may result, but only at the cost of increased buprenorphine toxicity. In order to elucidate the appeal of the benzodiazepine-buprenorphine combination, the present study looked at its neuropsycho-pharmacological effects on various emotional and cognitive parameters in the mouse. On the basis of previous dose-response studies, the regimen used was buprenorphine 0.3mg/kg, s.c. plus dipotassium clorazepate 1, 4 and 16 mg/kg, i.p. Anxiety-like behaviour was assessed using the black and white test box, and memory processes were examined via the spontaneous alternation paradigm in the Y-maze, and passive avoidance tests. Spontaneous locomotor activity was also evaluated. High doses of clorazepate impaired buprenorphine-induced hyperactivity and anxiogenic-like effects. They also increased buprenorphine-induced spontaneous alternation impairment, but did not modify its impact on long-term memory processes. These results suggest that the positive reinforcement experienced with the buprenorphine-benzodiazepine combination may be attributable, at least in part, to an increase in buprenorphine's sedative effect associated with a decrease in anxiogenicity.

Animals↗
PubMed2006

Competitive displacement binding assay on rat brain sections and using a beta-imager: application to mu-opioid ligands.

A new approach of competitive displacement binding assay using brain sections and a beta-imager is presented to estimate binding parameters such as affinity and selectivity of new compounds or to characterize receptor families or subtypes of receptors in small brain regions. This method includes a preliminary saturation assay intended to define the optimal concentration of displaceable radio-labeled ligand followed by the determination of displacement constants (IC(50) and K(i)) in cerebral regions rich in studied receptor. The technique application was demonstrated in seven rat brain structures, using displacement of the selective tritiated mu-opioid ligand [(3)H]-DAMGO by six opioid ligands: a specific agonist (DAMGO), less specific agonists (morphine, remifentanil), a non-specific antagonist with good affinity for mu receptors (naloxone) and ligands specific of other opioid subtypes (naltrindole, U50.488). Radioactivity counts were collected during 48 h. The assay-validation was performed by measuring intra- and inter-assay variation on determinations and by comparing presently obtained K(i) values with data from recognised methodologies. Both prove the accuracy of the proposed method.

Analgesics, Opioid↗
PubMed2005

Clorazepate affects cell surface regulation of delta and kappa opioid receptors, thereby altering buprenorphine-induced adaptation in the rat brain.

Concomitant abuse of buprenorphine (BPN) and benzodiazepines (BZD) may relate to a pharmacodynamic interaction between the two. The objective of the present work was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with BPN on selective kappa opiate tritiated ligand [3H]-U69 593 and delta opiate radioligand [3H]-deltorphine II binding in the rat brain. Bmax (maximal receptor density) and Kd (the dissociation constant) were directly determined at different brain regions of interest (ROI) selected for high densities of kappa and/or delta receptors in rats treated with BPN and/or CRZ. The agents were administered either once or for 21 consecutive days. Differences in Bmax and Kd (for both specific ligands) were related to drug treatment and receptor location. Globally, single BPN administration induced no changes in kappa or delta opiate receptor binding, whereas repeated BPN administration up-regulated kappa receptor density and decreased delta affinity. At the kappa receptor level, repeated administration of CRZ acted only on Kd, whereas the delta receptor was up-regulated. Repeated addition of CRZ to BPN had no effect on kappa receptor Bmax versus chronic controls. By significantly decreasing Bmax, CRZ nullified the effect of chronic BPN on the kappa receptor. The modifications were strongest in the nucleus accumbens, where both types of receptor occur. Treatments had region-selective effects in some brain areas, such as the amygdala, periaqueductal gray matter, hypothalamus and caudate putamen. Increased mu and delta receptor densities would be expected to provide reinforcement by enhancing reward, and impairment of kappa receptor availability would be expected to decrease aversion. The effects described are likely to influence addictive behavior among people abusing BZD and BPN.

Adaptation, Physiological↗
PubMed2005

Acute and chronic administration of clorazepate modifies the cell surface regulation of mu opioid receptors induced by buprenorphine in specific regions of the rat brain.

The aim of the present study was to investigate the acute and chronic effects of clorazepate (CRZ) alone or in combination with buprenorphine (BPN) on binding of the selective mu opiate tritiated ligand [3H]-DAMGO in the rat brain. Using 0.1 to 5 nM [3H]-DAMGO concentrations and a beta-imager, Bmax (maximal receptor density) and K(D) (the dissociation constant) were directly determined at different regions of interest (ROI) in the brains of rats treated with BPN and/or CRZ administered either once or over 21 consecutive days. Differences in Bmax and K(D) were related to both treatment and location. Acute BPN induced a down-regulation (62% mean decrease in Bmax observed on the whole brain) of mu opiate receptors. CRZ induced a mean 39% decrease in Bmax associated with substantially decreased affinity, particularly after acute administration (136% mean K(D) increase). Addition of CRZ to BPN [mean Bmax decreases of 34% (acute) and 29% (chronic)] induced significantly less down-regulation than did BPN alone, while altering affinity. These changes were maximal in the amygdaloid nucleus. Significant and persistent decreases in Bmax and affinity were also detected in the hippocampus, hypothalamus and thalamus. In the thalamus, an opposite regulation of Bmax was observed that was maximal with the combination. As the regions where changes were greatest have been specifically implicated in memory and socio-emotional functions and/or vegetative and endocrine adaptations, there is reason to suspect that the addition of CRZ to BPN may have clinical consequences. On the one hand, it may have some impact on drug abuse and misuse behaviors towards treatments including heroin substitute and BZD, and on the other, amplify the BPN effect-particularly hedonic or toxic-mainly after sporadic BPN-BZD abuses. These pharmacodynamic findings may explain, at least in part, the well-established preference of patients for the BPN-benzodiazepine combination and the toxicity with which it is associated.

Animals↗
PubMed2004

Erythropoietin and renin as biological markers in critically ill patients.

INTRODUCTION: During sepsis the endocrine, immune and nervous systems elaborate a multitude of biological responses. Little is known regarding the mechanisms responsible for the final circulating erythropoietin (EPO) and renin levels in septic shock. The aim of the present study was to assess the role of EPO and renin as biological markers in patients with septic shock. METHODS: A total of 44 critically ill patients with septic shock were evaluated. RESULTS: Nonsurvivors had significantly higher serum EPO levels than did survivors on admission (median [minimum-maximum]; 61 [10-602] versus 20 [5-369]). A negative relationship between serum EPO and blood haemoglobin concentrations was observed in the survivor group (r = -0.61; P < 0.001). In contrast, in the nonsurvivors the serum EPO concentration was independent of the blood haemoglobin concentration. Furthermore, we observed significant relationships between EPO concentration and lactate (r = 0.5; P < 0.001), arterial oxygen tension/fractional inspired oxygen ratio (r = -0.41; P < 0.005), arterial pH (r = -0.58; P < 0.001) and renin concentration (r = 0.42; P < 0.005). With regard to renin concentration, significant correlations with lactate (r = 0.52; P < 0.001) and arterial pH (r = -0.33; P < 0.05) were observed. CONCLUSION: Our findings show that EPO and renin concentrations increased in patients admitted to the intensive care unit with septic shock. Renin may be a significant mediator of EPO upregulation in patients with septic shock. Further studies regarding the regulation of EPO expression are clearly warranted.

Aged↗
PubMed2003

Dopamine: a key regulator to adapt action, emotion, motivation and cognition.

Dopamine is expressed in restricted brain areas involved in numerous integrative functions contributing to automated behaviours that are highly adaptive. During ontogenesis, dopamine can have a trophic action, which influences cortical specification directly, especially in prefrontal areas. Such a role is attested by the close relationships existing between the development of dopamine cortical innervation and cognitive abilities. Interestingly, such a proposal is reinforced by phylogenetic data. During the last stages of evolution in mammals, the characteristic extension of dopamine cortical innervation is also correlated with the development of cognitive capacities. More generally, the contribution of dopamine will be to increase the processing of cortical information through basal ganglia, either during the course of evolution or development. In this respect, dysmaturation suspected in schizophrenia and attention deficit-hyperactivity disorder in children can emphasize such a defect in basal ganglia processing. Remarkably, these diseases are improved by dopamine antagonists and agonists, respectively. In this line of evidence, experimental studies showed that selective lesions of the dopamine neurones in rats or primates can actually provide motor, limbic and cognitive deficits, in later cases especially when the mesocorticolimbic dopamine pathways are altered. Data resulting from lesion studies also showed significant alteration in attentional processes, thus raising the question of the direct involvement of dopamine in regulating attention. Dopamine can act as a powerful regulator and integrator of different aspects of brain functions. For example, in Parkinson's disease, besides motor impairment, dopamine degeneration is also expressed by alterations of both limbic, executive and cognitive functions, both improved by dopamine receptor agonists and dopa therapy. Dopamine has thus to be considered as a key regulator that contributes to behavioural adaptation and to the anticipatory processes necessary for preparing voluntary action consequent upon intention. In this respect, the alteration of dopamine transmission with age could contribute to cognitive impairment. Therefore, to normalize dopamine transmission pharmacologically could actually improve the cognitive and limbic deficits during normal aging, as it does in psychiatric and neurological disorders.

Animals↗