Serotonergic lesions alter cocaine-induced locomotor behavior and stress-activation of the mesocorticolimbic dopamine system

Morrow, Bret A.; Roth, Robert H.

doi:10.1002/(sici)1098-2396(199607)23:3<174::aid-syn6>3.0.co;2-5

Cited by 41 publications

(10 citation statements)

References 24 publications

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“…In that study, systemic administration of LY379268 increased non-evoked levels of 5-HT by 179% in the presence of citalopram (Cartmell et al 2001). Lesions of the dorsal raphe nuclei have been shown to increase DA metabolism in the mPFC (Morrow and Roth 1996), indicating a role for 5-HT transmission in maintaining appropriate DA responses in this brain region. It is important to note that immobilization-mediated increases in NA and DA witnessed in this report in the presence of citalopram are comparable to those in its absence.…”

Section: Discussionmentioning

confidence: 85%

The mGlu2/3 receptor agonist, LY354740, blocks immobilization‐induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex

Swanson

Perry

Schoepp

2003

Journal of Neurochemistry

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The metabotropic glutamate (mGlu2/3) receptor agonist, LY354740, exhibits anxiolytic-like properties in a number of rodent models. The present study utilized in vivo microdialysis to examine the effects of LY354740 on extracellular monoamine levels in the medial prefrontal cortex (mPFC) of animals subjected to 30 min immobilization stress. Immobilization stress significantly elevated extracellular levels of noradrenaline (NA) and dopamine (DA) in the mPFC, while systemic administration of LY354740 (30 mg/kg, s.c.) significantly attenuated immobilization-induced increases in both NA and DA. Reverse-dialysis of LY354740 (30 lM) into the mPFC significantly attenuated immobilization-induced increases in NA, but not DA without affecting basal levels of either amine.In separate studies in the presence of citalopram (1 lM; reverse dialysis into the mPFC), systemic administration of LY354740 attenuated immobilization-induced increases in NA and DA, but had no effect on serotonin (5-HT) levels. Co-administration of the selective mGlu2/3 receptor antagonist, LY341495, partially or fully reversed the attenuation in NA and DA levels produced by LY354740, respectively. Taken together, these data suggest that LY354740 may produce anti-stress actions, in part, by blocking stress-related increases in catecholamines in the mPFC via mGlu2/3 receptor stimulation.

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Section: Discussionmentioning

confidence: 85%

The mGlu2/3 receptor agonist, LY354740, blocks immobilization‐induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex

Swanson

Perry

Schoepp

2003

Journal of Neurochemistry

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“…Activation of the mesolimbic DA system, consisting of projections from the midbrain ventral tegmental area (VTA) to forebrain regions, including the nucleus accumbens (NAcc), is considered a critical event underlying the psychostimulant and reinforcing effects of cocaine (Wise, 1984). In general, activation of the serotonergic system appears to inhibit these effects of cocaine, whereas manipulations that decrease serotonergic transmission increase the psychostimulant and reinforcing properties of cocaine (Carroll et al, 1990;Loh and Roberts, 1990;Morrow and Roth, 1996;Herges and Taylor, 1999). Serotonergic neurons in the dorsal raphe project to the VTA and the NAcc (Azmitia and Segal, 1978;Herve et al, 1987;Van Bockstaele et al, 1994;Van Bockstaele et al, 1996) and influence dopaminergic transmission (Herve et al, 1979;Kelland et al, 1993;Prisco and Esposito, 1995;Brodie and Bunney, 1996), suggesting that regulation of mesolimbic dopaminergic activity may play an important role in the serotonergic modulation of cocaine effects.…”

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confidence: 99%

Enhanced Locomotor, Reinforcing, and Neurochemical Effects of Cocaine in Serotonin 5-Hydroxytryptamine 2C Receptor Mutant Mice

et al. 2002

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Brain serotonin [5-hydroxytryptamine (5-HT)] systems substantially influence the effects of cocaine; however, the contributions of individual 5-HT receptor subtypes to the regulation of cocaine responses are unclear. A line of mutant mice devoid of 5-HT2C receptors was used to examine the contribution of this receptor subtype to the serotonergic modulation of cocaine responses. Mutants display enhanced exploration of a novel environment and increased sensitivity to the locomotor stimulant effects of cocaine. In an operant intravenous self-administration model under a progressive ratio schedule of reinforcement, mutants display elevated levels of lever pressing for cocaine injections, indicating that the drug is more reinforcing in these mice. Moreover, mutants exhibit enhanced cocaine-induced elevations of dopamine (DA) levels in the nucleus accumbens, a brain region implicated in the stimulant and rewarding properties of cocaine. In contrast, phenotypic differences in dorsal striatal DA levels were not produced by cocaine treatment. These findings strongly implicate 5-HT2C receptors in the serotonergic suppression of DA-mediated behavioral responses to cocaine and as a potential therapeutic target for cocaine abuse.

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“…In the present experiment, group MDMA-20 exhibited substantial depletions of 5-HT and 5-HIAA, raising the possibility that 5-HT depletion contributes to the enhanced self-administration of cocaine observed in group MDMA-20. Additional support for this hypothesis derives from the observations that 5-HT depletion, induced by 5,7-dihydroxytryptamine, increases responding for cocaine maintained on a progressive ratio schedule of reinforcement (Loh and Roberts 1990), and enhances the acute locomotor response to a cocaine challenge (Morrow and Roth 1996). However, several other observations indicate that the effects of 5-HT depletion on cocaine-induced behaviors are not so clear cut.…”

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confidence: 99%

Pre-Exposure to (±)3,4-methylenedioxy-methamphetamine (MDMA) Facilitates Acquisition of Intravenous Cocaine Self-Administration in Rats

Fletcher

Robinson

Slippoy

2001

Neuropsychopharmacology

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Pre-exposure to ( Ϯ )3,4-methylenedioxymeth-amphetamine (MDMA) elevates locomotor activity and extracellular dopamine levels in the nucleus accumbens following a cocaine challenge. The present study determined whether MDMA-induced sensitization to the effects of cocaine could be demonstrated in rats selfA large body of evidence indicates that the reinforcing effect of cocaine is dependent in part upon increased dopamine (DA) transmission, particularly within the mesolimbic DA pathway terminating in the nucleus accumbens. Neurochemical studies have shown that at self-administered doses, cocaine increases extracellular DA levels in the nucleus accumbens (Pettit and Justice 1991;Di Ciano et al. 1995). Lesion studies have demonstrated that depletion of DA within the nucleus accumbens abolishes self-administration of cocaine (Roberts et al. 1977(Roberts et al. , 1980Pettit et al 1984). Similarly, pharmacologic studies indicate that injection of DA receptor antagonists in the nucleus accumbens increases intrave- nous self-administration of cocaine (Maldonado et al. 1993;Caine et al. 1995).The response of the mesolimbic dopamine system to cocaine, or such other psychomotor stimulants as amphetamine, can be influenced by previous drug exposure. Repeated intermittent injections of either cocaine or amphetamine result in an augmentation of the behavioral effects of a subsequent challenge dose of cocaine or amphetamine. The development of such sensitization is accompanied by a variety of adaptations in the functioning of mesolimbic neurons, including an increase in the ability of psychomotor stimulants to elevate extracellular levels of dopamine in the nucleus accumbens (reviewed in Kalivas and Stewart 1991;Kalivas et al 1993;Pierce and Kalivas 1997). Although the behavioral manifestation of sensitization has been most thoroughly studied in the context of locomotor activity, a number of studies indicate that the acquisition of cocaine or amphetamine self-administration can be enhanced by previous experience with these drugs (Horger et al. 1990(Horger et al. , 1992Valadez and Schenk 1994;Pierre and Vezina 1997;Lorrain et al. 2000). The results of these studies suggest that the reinforcing effects of cocaine and amphetamine are increased in animals previously exposured to these drugs.The amphetamine derivative ( Ϯ )3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") shares some stimulant properties with both amphetamine and cocaine (Gold et al. 1989;Geyer and Callaway 1994;Green et al. 1995;White et al. 1996). One of these similarities is that rats treated with MDMA may subsequently show augmented responses to psychomotor stimulants. Repeated treatment with MDMA (20 mg/ kg, twice a day for 4 days) augments the locomotor stimulant properties of amphetamine (Callaway and Geyer 1992) and of cocaine (Kalivas et al. 1998). Using the same treatment regimen, extracellular levels of dopamine in the nucleus accumbens were elevated in MDMA-treated rats following a cocaine challenge (Morgan et al. 1997), an effect similar to that obser...

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Serotonergic lesions alter cocaine-induced locomotor behavior and stress-activation of the mesocorticolimbic dopamine system

Cited by 41 publications

References 24 publications

The mGlu2/3 receptor agonist, LY354740, blocks immobilization‐induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex

The mGlu2/3 receptor agonist, LY354740, blocks immobilization‐induced increases in noradrenaline and dopamine release in the rat medial prefrontal cortex

Enhanced Locomotor, Reinforcing, and Neurochemical Effects of Cocaine in Serotonin 5-Hydroxytryptamine 2C Receptor Mutant Mice

Pre-Exposure to (±)3,4-methylenedioxy-methamphetamine (MDMA) Facilitates Acquisition of Intravenous Cocaine Self-Administration in Rats

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