Evaluating a Possible Pharmacokinetic Interaction between Remifentanil and Esmolol in the Rat

Haidar, Sam; Moreton, J. Edward; Liang, Zhongming; Hoke, John F.; Muir, Keith T.; Eddington, Natalie D.

doi:10.1021/js970079e

Cited by 35 publications

(25 citation statements)

References 31 publications

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“…To that end, we investigated the involvement of AcbC ACh activation during the conditioning to the physiologicalreinforcer food (ie sweetened condensed milk) and compared it to AcbC ACh activation by morphine (MOR), a prototypical drug of abuse that belongs to the same pharmacological class as RMF, a m-opioid receptor agonist, but is pharmacokinetically very different from RMF. MOR elimination from rat plasma is biphasic with an initial t 1/2 of 21 min (90% of total MOR; our own recalculation of the data obtained by Bhargava et al (1993a, b, c) and a terminal t 1/2 of 222 min (Bhargava et al, 1993b), whereas RMF's (monophasic) elimination half-life in rat blood/plasma ranges from 0.3 min (single dose; Crespo et al, 2005) to 0.69-0.75 min (postinfusion; Cox et al, 1999;Haidar et al, 1997). Unfortunately, comparative MOR-vs-RMF data on the distribution into brain areas are not available at a satisfactory temporal resolution.…”

Section: Introductionmentioning

confidence: 62%

Nucleus Accumbens Core Acetylcholine is Preferentially Activated During Acquisition of Drug- vs Food-Reinforced Behavior

Crespo

Stöckl

Zorn

et al. 2008

Neuropsychopharmacol

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Acquisition of drug-reinforced behavior is accompanied by a systematic increase of release of the neurotransmitter acetylcholine (ACh) rather than dopamine, the expected prime reward neurotransmitter candidate, in the nucleus accumbens core (AcbC), with activation of both muscarinic and nicotinic ACh receptors in the AcbC by ACh volume transmission being necessary for the drug conditioning. The present findings suggest that the AcbC ACh system is preferentially activated by drug reinforcers, because (1) acquisition of foodreinforced behavior was not paralleled by activation of ACh release in the AcbC whereas acquisition of morphine-reinforced behavior, like that of cocaine or remifentanil (tested previously), was, and because (2) local intra-AcbC administration of muscarinic or nicotinic ACh receptor antagonists (atropine or mecamylamine, respectively) did not block the acquisition of food-reinforced behavior whereas acquisition of drug-reinforced behavior had been blocked. Interestingly, the speed with which a drug of abuse distributed into the AcbC and was eliminated from the AcbC determined the size of the AcbC ACh signal, with the temporally more sharply delineated drug stimulus producing a more pronounced AcbC ACh signal. The present findings suggest that muscarinic and nicotinic ACh receptors in the AcbC are preferentially involved during reward conditioning for drugs of abuse vs sweetened condensed milk as a food reinforcer.

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Section: Introductionmentioning

confidence: 62%

Nucleus Accumbens Core Acetylcholine is Preferentially Activated During Acquisition of Drug- vs Food-Reinforced Behavior

Crespo

Stöckl

Zorn

et al. 2008

Neuropsychopharmacol

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“…Pharmacokinetic models generally describe plasma drug concentration with a bi-exponential decay accounting for redistribution of drug to a generalized peripheral compartment, plus systemic elimination of drug. However, measured blood concentrations of remifentanil in the rat exhibit rapid, single exponential decay (Haidar et al, 1997).…”

Section: Discussionmentioning

confidence: 98%

Remifentanil administration reveals biphasic phMRI temporal responses in rat consistent with dynamic receptor regulation

et al. 2007

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Many pharmacological stimuli influence multiple neurotransmitter systems in the brain, and the dynamics of the functional brain response can vary regionally. In this study, the temporal response of cerebral blood volume (CBV) was employed to spatially segment cerebral effects due to infusion of a potent mu-opioid receptor agonist. Repeated intravenous injection of 10 ug/kg remifentanil in rats caused reproducible regional positive, negative, and biphasic changes in CBV. Three temporal processes were identified in the cerebral response and analyzed within the framework of the general linear model. Firstly, a slow component identified CBV changes that were almost exclusively negative, and the spatial distribution was similar to the inhibition produced by morphine (200 ug/ kg). The largest CBV reductions occurred in caudate, accumbens, ventral hippocampus, cingulate, and piriform cortex. Secondly, a more rapid temporal component corresponded primarily with a regional distribution of positive changes in CBV consistent with GABAergic inhibition of hippocampal interneurons and associated projections. Thirdly, a response with the dynamics of mean arterial blood pressure correlated positively with CBV changes in hypothalamus, consistent with a central mechanism for control of blood pressure. We propose that the dominant source of the temporal variance in signal is dynamic modulation of drug targets by receptor endocytosis, an established effect in vitro. These results suggest that the temporal response of fMRI signal reflects underlying neurobiological processes, so that temporal decomposition strategies may aid interpretation of pharmacological mechanisms by identifying interconnected regions or those associated with common neural targets and processes.

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“…The white cue light at the end of the runway was also illuminated during the noncontingent condition. Intertrial intervals of 40 min (RMF) or 60 min (COC) were chosen to guarantee de facto elimination of the drug from the brain (Pan et al, 1991;Haidar et al, 1997;Hemby et al, 1997;Cox et al, 1999) before the start of the next trial. The operant level was determined with intravenous saline in another six rats, using a run-time cutoff of 60 s. Runway dimensions and experimental details have been published previously (Wakonigg et al, 2003a(Wakonigg et al, ,b, 2004.…”

Section: Methodsmentioning

confidence: 99%

Activation of Muscarinic and Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Core Is Necessary for the Acquisition of Drug Reinforcement

Crespo¹,

Šturm²,

Saria³

et al. 2006

J. Neurosci.

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Neurotransmitter release in the nucleus accumbens core (NACore) during the acquisition of remifentanil or cocaine reinforcement was determined in an operant runway procedure by simultaneous tandem mass spectrometric analysis of dopamine, acetylcholine, and remifentanil or cocaine itself. Run times for remifentanil or cocaine continually decreased over the five consecutive runs of the experiment. Intra-NACore dopamine, acetylcholine, and drug peaked with each intravenous remifentanil or cocaine self-administration and decreased to pre-run baseline with half-lives of ϳ10 min. As expected, remifentanil or cocaine peaks did not vary between the five runs. Surprisingly, however, drug-contingent dopamine peaks also did not change over the five runs, whereas acetylcholine peaks did. Thus, the acquisition of drug reinforcement was paralleled by a continuous increase in acetylcholine overflow in the NACore, whereas the overflow of dopamine, the expected prime neurotransmitter candidate for conditioning in drug reinforcement, did not increase. Local intra-accumbens administration by reverse microdialysis of either atropine or mecamylamine completely and reversibly blocked the acquisition of remifentanil reinforcement. Our findings suggest that activation of muscarinic and nicotinic acetylcholine receptors in the NACore by acetylcholine volume transmission is necessary during the acquisition phase of drug reinforcement conditioning.

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Evaluating a Possible Pharmacokinetic Interaction between Remifentanil and Esmolol in the Rat

Cited by 35 publications

References 31 publications

Nucleus Accumbens Core Acetylcholine is Preferentially Activated During Acquisition of Drug- vs Food-Reinforced Behavior

Nucleus Accumbens Core Acetylcholine is Preferentially Activated During Acquisition of Drug- vs Food-Reinforced Behavior

Remifentanil administration reveals biphasic phMRI temporal responses in rat consistent with dynamic receptor regulation

Activation of Muscarinic and Nicotinic Acetylcholine Receptors in the Nucleus Accumbens Core Is Necessary for the Acquisition of Drug Reinforcement

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