Microdialysis, in vivo

The basal dialysate concentrations in the striatum for the experiments were 11.1 0.96 fmol/min (n = 62). 

For comparison, administration of a s.c. dose of 0.1 pmol/kg and a p.o. dose of 10 pmol/kg of 5-OH-DPAT (9) induced very similar effects. Both treatments induced a significant decrease in dopamine release from 15 to 165 min with a maximum decrease in dopamine release of 70 % 

Footnotes a Experiment lasted 150 min. All other experiments lasted 165 min. All the AUCs of s.c. and p.o. doses of each compound were compared, but only the doses that were not significantly different were put in line in the table. 

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The comparatively straightforward link between 5-HT and its primary metabolite, 5-HIAA, encouraged many researchers to use changes in the ratio of tissue concentrations of 5-HIAA and 5-HT as an index of the rate of release of 5-HT ex vivo. However, it has been clear for some time that the majority of 5-HT is metabolised in the cytoplasm by MAO before it is released from 5-HT nerve terminals. Consequently, the reliability of the 5-HIAA 5-HT ratio as an index of transmitter release is rather dubious, although it could be used as an acceptable measure of MAO activity. In any case, the development of in vivo microdialysis means that changes in the concentration of extracellular 5-HT can now be monitored directly which, under drug-free conditions, provides a far more reliable indication of any changes in the rate of release of 5-HT. 

Petty, F, Jordan, S, Kramer, GL, Zukas, PK and Wu, J (1997) Benzodiazepine prevention of swim-stress induced sensitization of cortical biogenic amines an in vivo microdialysis study. Neurochem. Res. 22 1101-1104. 

A link between 5-HT release and increased waking is supported by evidence from in vivo microdialysis of cats and rats. This has confirmed that the extracellular concentration of 5-HT in all brain regions studied to date is lower during both SWS and REM sleep than in the awake state (see Portas, Bjorvatn and Ursin 2000). Interestingly, if behaviour is maintained at a constant level, the activity of 5-HT neurons does not show circadian variation although 5-HT turnover in the brain areas to which they project... 

Porkka-Heiskanen, T., Strecker, R. E. McCarley, R. W. (2000). Brain site-specificity of extracellular adenosine concentration changes during sleep deprivation and spontaneous sleep an in vivo microdialysis study. Neuroscience 99, 507-17. 

State-dependent release of acetylcholine in rat thalamus measured by in vivo microdialysis. J. Neurosci 14, 5236-42. 

Kodama, T., Lai, Y. Y. Siegel, J. M. (1998). Enhanced glutamate release during REM sleep in the rostromedial medulla as measured by in vivo microdialysis. Brain Res. 780, 178 81. 

EEG slow waves. The differential EEG and ACh responses to dialysis delivery of AF-DX 116 (M2/M4) versus pirenzepine (M1/M4) supports the conclusion that, in B6 mouse, postsynaptic muscarinic receptors of the Ml subtype form one receptor mechanism by which ACh activates the EEG (Douglas et al, 2002a). The data summarized in Fig. 5.11 provide direct measures of G protein activation in basal forebrain and prefrontal cortex by muscarinic cholinergic receptors (DeMarco et al, 2004). The in vitro data of Fig. 5.11A indicate the presence of functional muscarinic receptors in regions of B6 mouse prefrontal cortex where in vivo microdialysis studies (Douglas et al, 2002a, b) revealed modulation of ACh release and EEG by pre- and postsynaptic muscarinic receptors (Figs. 5.9 and 5.10). 

Strecker, R. E., Nalwalk, J., Dauphin, L. J. et al. (2002). Extracellular histamine levels in the feline preoptic/anterior hypothalamic area during natural sleep-wakefulness and prolonged wakefulness an in vivo microdialysis study. Neuroscience 113, 663-70. 

Figure 12.1 Extracellular adenosine concentrations in different brain areas, measured with in vivo microdialysis from cats during sleep deprivation (6 h gentle handling) and recovery sleep. Concentrations are given as a percentage of pre-deprivation values. BF, basal forebrain CX, cingulate cortex TH, VA/VL nucleus of thalamus POA, preoptic hypothalamic area DRN, dorsal raphe nucleus PPT, pedunculopontine nucleus. In BF and CX adenosine rises during sleep deprivation, but starts to decline during deprivation in CX, whereas the decline occurs during recovery in the BF. In other areas there is no accumulation during sleep deprivation. Modified from Porkka-Heiskanen et al. (2000).

Moghaddam, B., Roth, R.H., and Bunny, B.S., Characterization of dopamine release in the rat medial prefrontal cortex as assessed by in vivo microdialysis comparison to the striatum, Neuroscience, 36, 669, 1990. 

Robertson, G.S., Damsma, G., and Fibiger, H.C., Characterization of dopamine release in the substantia nigra by in vivo microdialysis in freely moving rats, J. Neurosci., 11, 2209, 1991. 

Hurd, Y.L., Weiss, F., Koob, G., and Ungerstedt, U., Cocaine reinforcement and extracellular dopamine overflow in the rat nucleus accumbens an in vivo microdialysis study, Brain Res., 498, 199, 1989. 

Pistis, M., Ferraro, L., Flore, G., Tanganelli, S., Gessa, G.L., and Devoto, P., Delta(9)-tetrahydrocan-nabinol decreases extracellular GABA and increases extracellular glutamate and dopamine levels in the prefrontal cortex an in vivo microdialysis study, Brain Res., 948, 155, 2002. 

Chen, J., Paredes, W., Lowinson, J.H., and Gardner, E.L., Strain-specific facilitation of dopamine efflux by A9-tetrahydrocannabinol in the nucleus accumbens of a rat an in vivo microdialysis study, Neurosci. Lett., 129, 136, 1991. 

Murai, T., Koshikawa, N., Kanayama, T., Takada, K., Tomiyama, K., and Kobayashi, M., Opposite effects of midazolam and beta-carboline-3-carboxylate ethyl ester on the release of dopamine from rat nucleus accumbens measured by in vivo microdialysis, Eur. J. Pharmacol., 261, 65, 1994. 

Rocher, C., Gardier, A.M. Effects of repeated systemic administration of d-fenflur amine on serotonin and glutamate release in rat ventral hippocampus comparison with methamphetamine using in vivo microdialysis. Naunyn Schmiedeberg s Arch. Pharmacol. 363 422, 2001. 

Spanagel R., Herz A., Shippenberg T. The effects of opioid peptides on dopamine release in the nucleus accumbens an in vivo microdialysis study. J. Neurochem. 55 1734, 1990. 

Figure 7.4 Dose-response effects of MDMA on extracellular levels of endogenous 5-HT (left panel) and DA (right panel) in rat nucleus accumbens. Male rats undergoing in vivo microdialysis received i.v. injections of 1 and 3 mg/kg MDMA at 0 and 60 min, respectively. Dialysate levels of 5-HT and DA were assayed by HPLC-ECD. Data are mean SEM, expressed as pg/5 pi sample, for N = 6 rats/group. Baseline levels of 5-HT and DA were 0.22 0.03 and 1.44 0.24 pg/5 pi, respectively. Significant with respect to pre-injection control (P < 0.05 Duncan s). See Baumann et al.39 for methods.

In vivo microdialysis has been used to evaluate the persistent neurochemical consequences of MDMA exposure in rats.88114-116 Series et al.114 carried out microdialysis in rat frontal cortex 2 weeks after a 4-day regimen of 20 mg/kg s.c. MDMA. Prior MDMA exposure did not affect baseline extracellular levels of 5-HT, but decreased levels of the 5-HT metabolite, 5-hydroxyin-doleacetic acid (5-HIAA), to 30% of control. Moreover, the ability of (+)-fenfluramine to evoke 5-HT release was markedly blunted in MDMA-pretreated rats. In an analogous investigation, Shankaran and Gudelsky115 assessed neurochemical effects of acute MDMA challenge in rats that had previously received 4 doses of 10 mg/kg i.p. MDMA. A week after MDMA pretreatment, baseline levels of dialysate 5-HT and DA in striatum were not altered even though tissue levels of 5-HT were depleted by 50%. The ability of MDMA to evoke 5-HT release was severely impaired in MDMA-pretreated rats while the concurrent DA response was normal. In this same study, effects... 

Baumann, M.H. and Rutter, J.J., Application of in vivo microdialysis methods to the study of psychomotor stimulant drugs, in Methods in Drug Abuse Research, Cellular and Circuit Level Analysis, Warerhouse, B.D., Ed., CRC Press, Boca Raton, FL, 2003, 51-86. 

Hall, F.S., Devries, A.C., Fong, G.W., Huang, S., and Pert, A., Effects of 5,7-dihydroxytryptamine depletion of tissue serotonin levels on extracellular serotonin in the striatum assessed with in vivo microdialysis relationship to behavior, Synapse 33(1), 16-25, 1999. 

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