Fluoxetine reduces intravenous cocaine self-administration in rats

Carroll, Marilyn E.; Sylvie, T.; Asencio, Marisel; Kragh, Rebecca

doi:10.1016/0091-3057(90)90232-7

Cited by 242 publications

(94 citation statements)

References 27 publications

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“…Several nonselective global manipulations that enhance 5-HT function, including L-tryptophan Smith et al, 1986) and fluoxetine (Carroll et al, 1990;Richardson and Roberts, 1991) also reduce cocaine, or amphetamine, self-administration on both FR and progressive ratio schedules. One implication of the present results is that these manipulations could act to reduce cocaine selfadministration via their ability to enhance 5-HT neurotransmission through 5-HT 2C receptors localized within the VTA.…”

Section: Discussionmentioning

confidence: 99%

Injection of the 5-HT2C Receptor Agonist Ro60-0175 into the Ventral Tegmental Area Reduces Cocaine-Induced Locomotor Activity and Cocaine Self-Administration

Fletcher

Chintoh

Sinyard

et al. 2003

Neuropsychopharmacol

122

100

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Previously, we have shown that systemic administration of the 5-HT 2C receptor agonist Ro60-0175 reduces cocaine-induced locomotor activity and cocaine self-administration. Ro60-0175 also alters the activity of midbrain dopamine (DA) neurons of the ventral tegmental area (VTA), a region where 5-HT 2C receptors are expressed. The present experiments investigated whether microinjections of Ro60-0175 into the VTA would alter the locomotor stimulant effect of cocaine and cocaine self-administration. In the tests for locomotor activity injection of 3 and 10, but not 1 mg, Ro60-0175 into the VTA reduced the locomotor stimulation resulting from injection of 10 mg/ kg cocaine. In tests of cocaine self-administration, rats were trained to lever press for intravenous infusions of 0.25 mg cocaine delivered on either a fixed ratio 5 (FR5) or a progressive ratio schedule. Intra-VTA injection of Ro60-0175 at doses of 3 and 10 mg reduced responding for cocaine on both schedules without significantly altering the latency to initiate responding or the rate of responding. A subsequent experiment determined that the suppressant effect of intra-VTA Ro60-0175 (3 mg) on responding for cocaine was prevented by pretreatment with the selective 5-HT 2C receptor antagonist SB242,084 (0.5 mg/kg). In a final experiment, intra-VTA injection of Ro60-0175 reduced responding for food reinforcement on the same progressive ratio schedule as used for cocaine selfadministration. These results demonstrate that stimulation of 5-HT 2C receptors in the VTA is sufficient to attenuate the stimulant and reinforcing effects of cocaine. These effects complement electrophysiological and neurochemical findings, and indicate that 5-HT 2C receptors localized within the VTA modulate the activity of mesolimbic DA neurons.

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Section: Discussionmentioning

confidence: 99%

Injection of the 5-HT2C Receptor Agonist Ro60-0175 into the Ventral Tegmental Area Reduces Cocaine-Induced Locomotor Activity and Cocaine Self-Administration

Fletcher

Chintoh

Sinyard

et al. 2003

Neuropsychopharmacol

122

100

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“…To this end, depletion of 5-HT by medial forebrain bundle lesions with 5,7-dihydroxytryptamine (5,7-DHT) increases the reinforcing efficacy of cocaine, ostensibly by elevating mesocorticolimbic DA levels (Loh and Roberts, 1990). Elsewhere, it has been shown that manipulations that increase 5-HT function decrease cocaine self-administration (Carroll et al, 1990;Glatz et al, 2002;Howell and Byrd, 1995), and there is a negative correlation between psychostimulant potency and binding affinity at the 5-HT transporter (SERT) site (Ritz and Kuhar, 1989). Thus, a compelling case can be made for MDMA/cocaine antagonism, at least at low to moderate levels of the drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Rothman and Baumann, 2003. The preferential action of MDMA at the SERT site is of particular significance because manipulations that increase 5-HT function decrease cocaine and amphetamine self-administration (Carroll et al, 1990;Howell and Byrd, 1995;Smith et al, 1986;Wee et al, 2005). In addition, single gene knockout of SERT has been shown to increase the rewarding properties of cocaine, ostensibly because stimulated actions at SERT are at least partially aversive (Uhl et al, 2002), or modulate DA activity (Hall et al, 2004).…”

mentioning

confidence: 99%

The effects of concurrent administration of (±)3,4-Methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat

Diller

Rocha

Cardon

et al. 2007

Pharmacology Biochemistry and Behavior

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Conditioned place preference (CPP), a commonly used model for studying the role of contextual cues in drug reward and drug seeking, was employed to explore possible behavioral interactions between (±)3,4-methylenedioxymethamphetamine (MDMA; "ecstasy") and cocaine. On each of four occasions, adult male rats received one of three doses of MDMA (0 mg/kg, 5 mg/kg, 10 mg/kg; administered subcutaneously [s.c.]) combined with one of three doses of cocaine (0 mg/kg, 2.5 mg/ kg, 5 mg/kg; administered intraperitoneally [i.p.]), and were then tested in a CPP paradigm. The results showed MDMA-induced CPP at a unit dose of 5 mg/kg, but at the 10 mg/kg dose there was a return to baseline (control) performance levels. For cocaine alone, CPP increased in a linear fashion as the drug dose was increased. Concurrent administration resulted in antagonism of each drug, but there was evidence that this pattern was reversible at higher doses of the respective drugs. These data are instructive insofar as they suggest that the behavioral and neurochemical effects of MDMA and cocaine presented in isolation are dramatically altered when the two drugs are presented in combination.

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“…Thus, increasing 5-HT levels generally inhibits cocaine self-administration (Carroll et al 1990;Richardson and Roberts 1991;Peltier and Schenk 1993;but see Porrino et al 1989;Tella 1995). Because cocaine-induced 5-HT release is reduced in SERT −/− mice and rats (Shen et al 2004; J.H., E.C., J.O., unpublished observations), because both SERT −/− mice and rats show increased cocaineinduced CPP (Sora et al 1998(Sora et al , 2001; present study), and because novelty-induced locomotor activity was comparable in SERT +/+ and SERT −/− rats, cocaine supersensitivity in SERT −/− models may be explained by reduced 5-HT dampening of the cocaine's effects.…”

Section: Enhanced Rewarding Properties Of Cocaine In Sertmentioning

confidence: 99%

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

et al. 2008

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Rationale While individual differences in vulnerability to psychostimulants have been largely attributed to dopaminergic neurotransmission, the role of serotonin is not fully understood. Objectives To study the rewarding and motivational properties of cocaine in the serotonin transporter knockout (SERT −/− ) rat and the involvement of compensatory changes in 5-HT 1A receptor function are the objectives of the study. Materials and methodsThe SERT −/− rat was tested for cocaine-induced locomotor activity, cocaine-induced conditioned place preference, and intravenous cocaine selfadministration. In addition, the function and expression of 5-HT 1A receptors was assessed using telemetry and autoradiography, respectively, and the effect of 5-HT 1A receptor ligands on cocaine's psychomotor effects were studied.Results Cocaine-induced hyperactivity and conditioned place preference, as well as intravenous cocaine selfadministration were enhanced in SERT −/− rats. Furthermore,

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Fluoxetine reduces intravenous cocaine self-administration in rats

Cited by 242 publications

References 27 publications

Injection of the 5-HT2C Receptor Agonist Ro60-0175 into the Ventral Tegmental Area Reduces Cocaine-Induced Locomotor Activity and Cocaine Self-Administration

Injection of the 5-HT2C Receptor Agonist Ro60-0175 into the Ventral Tegmental Area Reduces Cocaine-Induced Locomotor Activity and Cocaine Self-Administration

The effects of concurrent administration of (±)3,4-Methylenedioxymethamphetamine and cocaine on conditioned place preference in the adult male rat

Adaptations in pre- and postsynaptic 5-HT1A receptor function and cocaine supersensitivity in serotonin transporter knockout rats

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