Effects of Midazolam and Flunitrazepam on the Release of Dopamine From Rat Striatum Measured by in Vivo Microdialysis

Takada, Koji; Murai, Tameatsu; Kanayama, T; Koshikawa, Noriaki

doi:10.1093/bja/70.2.181

Cited by 72 publications

(45 citation statements)

References 19 publications

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“…Interestingly, so far benzodiazepines have not been shown to increase dopamine levels in the NAc as determined by dialysis, at least after acute administration. On the contrary, a number of studies showed a reduction in the extracellular dopamine concentrations in NAc following the systemic administration of benzodiazepines (Invernizzi et al, 1991;Finlay et al, 1992;Takada et al, 1993), a paradoxical finding considering the modest but well-documented reinforcing actions of benzodiazepines in humans and laboratory animals (see Licata and Rowlett (2008) for a review). This could indicate that benzodiazepines affect the mesolimbic dopamine system differently than other drugs of abuse, for example, by simultaneously modulating multiple sites in this circuit, and/or that benzodiazepines may exert their effects through routes that do not directly involve dopamine signaling.…”

Section: Discussionmentioning

confidence: 99%

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Engin

Bakhurin

Smith

et al. 2014

Neuropsychopharmacol

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Despite long-standing concerns regarding the abuse liability of benzodiazepines, the mechanisms underlying properties of benzodiazepines that may be relevant to abuse are still poorly understood. Earlier studies showed that compounds selective for a1-containing GABA A receptors (a1GABA A Rs) are abused by humans and self-administered by animals, and that these receptors may underlie a preference for benzodiazepines as well as neuroplastic changes observed in the ventral tegmental area following benzodiazepine administration. There is some evidence, however, that even L-838, 417, a compound with antagonistic properties at a1GABA A Rs and agonistic properties at the other three benzodiazepine-sensitive GABA A receptor subtypes, is self-administered, and that the a2GABA A Rs may have a role in benzodiazepine-induced reward enhancement. Using a two-bottle choice drinking paradigm to evaluate midazolam preference and an intracranial self-stimulation (ICSS) paradigm to evaluate the impact of midazolam on reward enhancement, we demonstrated that mice carrying a histidine-to-arginine point mutation in the a2 subunit which renders it insensitive to benzodiazepines (a2(H101R) mice) did not prefer midazolam and did not show midazolam-induced reward enhancement in ICSS, in contrast to wild-type controls, suggesting that a2GABA A Rs are necessary for the reward enhancing effects and preference for oral benzodiazepines. Through a viral-mediated knockdown of a2GABA A Rs in the nucleus accumbens (NAc), we demonstrated that a2 in the NAc is necessary for the preference for midazolam. Findings imply that a2GABA A Rs in the NAc are involved in at least some rewardrelated properties of benzodiazepines, which might partially underlie repeated drug-taking behavior.

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Section: Discussionmentioning

confidence: 99%

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Engin

Bakhurin

Smith

et al. 2014

Neuropsychopharmacol

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“…administered 24 h before commencing EM-2 infusion. The doses used were based on the outcome of previously reported experiments (EM-2 and EM-1: Sakurada et al, 2001;TTX: Fusa et al, 2002;Saigusa et al, 2001;Takada et al, 1993;Tomiyama et al, 1993Tomiyama et al, , 1995CTOP: Yoshida et al, 1999;naloxone: Yoshida et al, 1999;naloxonazine: Piepponen and Ahtee, 1995). The reported doses of EM-2 and EM-1 were the amount (nmol) of compounds in 25 min perfusion liquid (50 ml) and the dose of CTOP was the amount of the compound in 50 min perfusion liquid (100 ml).…”

Section: Drugsmentioning

confidence: 99%

“…Fusa et al, 2002cf. Fusa et al, , 2005Murai et al, 1994;Saigusa et al, 1997Saigusa et al, , 1999Takada et al, 1993;Tomiyama et al, 1993Tomiyama et al, , 1995.…”

Section: Introductionunclassified

Endomorphin-2 and Endomorphin-1 Promote the Extracellular Amount of Accumbal Dopamine via Nonopioid and Mu-Opioid Receptors, Respectively

Okutsu

Watanabe

Takahashi

et al. 2005

Neuropsychopharmacol

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Activation of mu-opioid receptors in the nucleus accumbens (NAc) is known to increase accumbal dopamine efflux in rats. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH 2 ; EM-2) and endomorphin-1 (Tyr-Pro-Trp-Phe-NH 2 ; EM-1) are suggested to be the endogenous ligands for the mu-opioid receptor. As the ability of EM-2 and EM-1 to alter the accumbal extracellular dopamine level has not yet been studied in freely moving rats, the present study was performed, using a microdialysis technique that allows on-line monitoring of the extracellular dopamine with a temporal resolution of 5 min. A 25 min infusion of either EM-2 or EM-1 into the NAc (5, 25, and 50 nmol) produced a dose-dependent increase of the accumbal dopamine level. The EM-2 (50 nmol)-and EM-1 (25 and 50 nmol)-induced dopamine efflux were abolished by intra-accumbal perfusion of tetrodotoxin (2 mM). Intra-accumbal perfusion of the mu-opioid receptor antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH 2 ; 3 nmol) failed to affect the EM-2 (50 nmol)-induced dopamine release, whereas it significantly inhibited the EM-1 (25 and 50 nmol)-induced dopamine release. The EM-1 (50 nmol)-induced accumbal dopamine efflux was significantly reduced by the systemic administration of the putative mu1-opioid receptor antagonist naloxonazine (15 mg/kg, intraperitoneally (i.p.), given 24 h before starting the perfusion). Systemic administration of the aspecific opioid receptor antagonist naloxone (1 mg/kg, i.p., given 10 or 20 min before starting the perfusion) also failed to affect the EM-2 (50 nmol)-induced dopamine efflux, whereas it significantly inhibited the EM-1 (25 and 50 nmol)-induced dopamine efflux. The present study shows that the intra-accumbal infusion of EM-2 and EM-1 increases accumbal dopamine efflux by mechanisms that fully differ. It is concluded that the effects of EM-2 are not mediated via opioid receptors in contrast to the effects of EM-1 that are mediated via mu1-opioid receptors in the NAc.

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“…Previous studies in which an identical dialysis technique was used (Takada et al, 1993;Tomiyama et al, 1993) have shown that the baseline dopamine concentration mea sured in the dialysate of striatally perfused rats which received their implantation at least 7 days earlier, is largely dependent on neuronal activity as more than 80% of the dopamine release has been found to be tetrodotoxin-sensitive and Ca2 '^dependent. The results of the present study show that stimulation of acetylcholine or dopamine recep tors in the nucleus accumbens produced significant changes in this dopamine release in the ventrolateral striatum.…”

Section: Discussionmentioning

confidence: 99%

“…The dialysis probe technique assessed in the present study has been described and validated in previous studies of our group (Takada et al, 1993;Tomiyama et al, 1993). Below, a short description is given.…”

Section: 1 Animals and Surgerymentioning

confidence: 99%

Stimulation of acetylcholine or dopamine receptors in the nucleus accumbens differentially alters dopamine release in the striatum of freely moving rats

Koshikawa

Yoshida

Kitamura

et al. 1996

European Journal of Pharmacology

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The present study examined whether unilateral stimulation of acetylcholine or dopamine receptors in the nucleus accumbens induces an asymmetry in dopamine transmission in the ventrolateral striatum. For this purpose, a microdialysis technique was used to measure dopamine release in both sides of the ventrolateral striatum following unilateral injections of carbachol (5 ¿¿g/0.5 j j l \ ) or a mixture of dopamine Dj and dopamine D 2 receptor agonists (l-phenyl-2,3,4,5-tetrahydro-ltf-3-benzazepine-7,8-diol 5 fig + quinpirole 10 ¿¿g/0.5 /xl) into the nucleus accumbens. The results show that carbachol injection increased dopamine release in the ipsilateral striatum without changing dopamine release in the contralateral striatum, whereas the dopamine D , / D 2 receptor agonist mixture injected unilaterally into the nucleus accumbens produced an increase followed by a decrease in dopamine release in the ipsilateral striatum, but only a decrease in dopamine release in the contralateral striatum. The biochemical effects of the cholinergic treatment greatly outlasted the drug-induced contralateral turning, whereas the biochemical effects of the dopaminergic treatment showed a good correlation with the drug-induced contralateral turning. The present study provides biochemical evidence that unilateral stimulation of acetylcholine or dopamine receptors in the nucleus accumbens elicits an asymmetry in dopaminergic activity in the ventrolateral striatum. The present study also provides biochemical evidence that two distinct neural substrates are involved in the effects of cholinergic and dopaminergic manipulation of the nucleus accumbens.

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Effects of Midazolam and Flunitrazepam on the Release of Dopamine From Rat Striatum Measured by in Vivo Microdialysis

Cited by 72 publications

References 19 publications

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Neural Basis of Benzodiazepine Reward: Requirement for α2 Containing GABAA Receptors in the Nucleus Accumbens

Endomorphin-2 and Endomorphin-1 Promote the Extracellular Amount of Accumbal Dopamine via Nonopioid and Mu-Opioid Receptors, Respectively

Stimulation of acetylcholine or dopamine receptors in the nucleus accumbens differentially alters dopamine release in the striatum of freely moving rats

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