Extracellular dopamine, norepinephrine, and serotonin in the ventral tegmental area and nucleus accumbens of freely moving rats during intracerebral dialysis following systemic administration of cocaine and other uptake blockers

Abstract

Extracellular levels of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) were measured by microdialysis in conscious rats equipped with dual probes, one in the ventral tegmental area (VTA) and another one in the contralateral nucleus accumbens (NACC). Dialysate content of all amines in both regions was essentially abolished by local infusion of tetrodotoxin (1 microM) or Ca2+-free buffer. Injection of the selective DA uptake blocker GBR 12935 (15 mg/kg i.p.) increased DA, as well as NE and, to a lesser extent, 5-HT in the VTA; it increased DA more than 5-HT in the NACC. The selective NE uptake blocker desipramine (10 mg/kg i.p.) increased NE but also 5-HT in the VTA and NACC; the DA level was persistently enhanced in the VTA, whereas in the NACC it initially rose and then fell below baseline value. The selective 5-HT uptake blocker citalopram (15 mg/kg i.p.) was generally more effective in elevating dialysate level of 5-HT than that of other amines in both regions. Cocaine (20 mg/kg i.p.) was non-selective in enhancing all three amines in both regions. There is considerable crosstalk between monoamine systems occurring upon systemic administration of uptake blockers, and the VTA and NACC are notably different in the time course of the DA effect (long-lasting versus transient).

Effects of cocaine on monoamine uptake as measured ex vivo

“…This result is consistent with results of both in vitro and in vivo studies with GBR 12909 [12,3]. Similarly, our results with DMI and citalopram are consistent with existing in vitro [11,24] and in vivo [19,17] results.…”

“…cocaine. This is consistent with studies using in vivo microdialysis [19] and supports an in vivo mechanism of blockade of NE uptake by cocaine. It has also well established that cocaine can block the uptake of 5-HT in vitro [22].…”

“…Research with in vivo microdialysis has demonstrated an increase in monoamine concentrations in rat striatum and nucleus accumbens following cocaine administration [19], and in monkey striatum as well [29]. Experiments utilizing in vivo electrochemistry have reported that systemic administration of cocaine can decrease the clearance of locally-applied dopamine in Address all correspondence to: Zhixia Wang, M.D., Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA 39216, Phone: (601) 815-1022 FAX (601) 984-5899, E-mail: ZWang@psychiatry.umsmed.edu.…”

“…Research with in vivo microdialysis has demonstrated an increase in monoamine concentrations in rat striatum and nucleus accumbens following cocaine administration [19], and in monkey striatum as well [29]. Experiments utilizing in vivo electrochemistry have reported that systemic administration of cocaine can decrease the clearance of locally-applied dopamine in rat striatum and accumbens [4,38], suggesting that blockade of uptake underlies the monoamine elevations.…”

Administration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats

“…Cocaine decreases dopamine reuptake by inhibiting the dopamine transporter in the mesolimbic system, an effect thought to be critical for self-administration and other behaviors associated with cocaine reinforcement (Goeders and Smith 1983;Karler et al 1989;Ritz et al 1987;RoddHenricks et al 2002). In addition, cocaine administration can increase extracellular glutamate, serotonin and norepinephrine levels in various brain regions (Di Chiara and Imperato 1988;Kalivas and Duffy 1995;Reid et al 1997;Reith et al 1997). Cocaine-mediated increases in levels of dopamine and other neurotransmitters can alter the activity of downstream signaling proteins such as the dopamine-and cAMP regulated phosphoprotein-32 (DARPP32), cAMP response element binding protein (CREB), and extracellular signal-regulated protein kinase (ERK) (Carlezon et al 1998;Greengard et al 1999;Mattson et al 2005;Miserendino and Nestler 1995;Self et al 1998;Terwilliger et al 1991).…”