Contribution of Serotonin (5-Hydroxytryptamine; 5-HT) 5-HT2 Receptor Subtypes to the Hyperlocomotor Effects of Cocaine: Acute and Chronic Pharmacological Analyses

  title={Contribution of Serotonin (5-Hydroxytryptamine; 5-HT) 5-HT2 Receptor Subtypes to the Hyperlocomotor Effects of Cocaine: Acute and Chronic Pharmacological Analyses},
  author={Małgorzata Filip and Marcy J. Bubar and Kathryn A. Cunningham},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={1246 - 1254}
The role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes (5-HT2AR, 5-HT2BR, and 5-HT2CR) in acute cocaine-evoked hyperactivity was compared with their contribution to the development and expression of locomotor sensitization upon repeated, intermittent treatment with cocaine (10 mg/kg/day for 5 days) in male Wistar rats. Cocaine-evoked hyperactivity was significantly enhanced by pretreatment with the preferential 5-HT2AR agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane… 

Figures and Tables from this paper

Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats
Analysis of the role of the 5-HT2R subtypes in the discriminative stimulus effects of cocaine indicates oppositional influence of 4-hydroxyphenyl)-1(2-fluorophenyl)-3-hydroxytryptamine-N′-(3-methyl-5-isothiazolyl)-2(E)-propene and 5- HT2CR may be important in modulating the subjectiveeffects of cocaine in humans.
Blockade of nucleus accumbens 5-HT2A and 5-HT2C receptors prevents the expression of cocaine-induced behavioral and neurochemical sensitization in rats
These data provide the first evidence that NAC 5-HT2A and 5- HT2C receptors are critical for the expression of cocaine-induced neuroplasticity following protracted withdrawal, which has relevance for their therapeutic utility in the treatment of addiction.
The effects of the 5-HT2C receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonists
SB242084 potentiated the locomotor stimulant effects of both indirect DA and 5-HT agonists and might reflect differences between changes in synaptic levels of 5- HT produced by release compared to reuptake inhibition.
Effects of 5-HT1A, 5-HT2A and 5-HT2C receptor agonists and antagonists on responding for a conditioned reinforcer and its enhancement by methylphenidate
5-HT2C receptor activity is an important modulator of DA-dependent reward-related behaviours, and exerted bidirectional modulation of responding for a CRf, especially when DA activity was increased.
The Serotonin 2C Receptor Antagonist SB 242084 Exhibits Abuse-Related Effects Typical of Stimulants in Squirrel Monkeys
These studies are the first to assess the direct reinforcing effects of a 5-HT2CR-selective antagonist in any species and suggest that SB 242084 exhibits a behavioral profile that is qualitatively similar to other psychostimulants, although its efficacy is modest compared with cocaine.
Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction.
The identification of synergism between a 5-HT(2A)R antagonist plus a5- HT(2C)R agonist to attenuate these factors important in relapse indicates the promise of a bifunctional ligand as an anti-addiction pharmacotherapeutic, setting the stage to develop new ligands with improved efficacy, potency, selectivity, and in vivo profiles over the individual molecules.


Antagonism of 5-hydroxytryptamine(2a) receptors attenuates the behavioral effects of cocaine in rats.
It is suggested that 5-HT2A receptors play an important role in the behavioral effects of cocaine and that they should be considered a viable target for analysis in the search for pharmacotherapies useful in the treatment of cocaine dependence.
Differential Regulation of the Mesoaccumbens Circuit by Serotonin 5-Hydroxytryptamine (5-HT)2A and 5-HT2CReceptors
These findings are the first to demonstrate that the behavioral effects of cocaine are generated in part by activation of 5-HT2ARs in the VTA and byactivation of 4-trifluoromethylphenylsulfon-amido)phenyl-5-oxopentyl in the NAc shell.
Modulation of the discriminative stimulus properties of cocaine by 5-HT1B and 5-HT2C receptors.
Several 5-HT receptor compounds do not substitute for cocaine, but not antagonists, differentially modulate the stimulus effects of cocaine.
Serotonin 5-HT2C receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine
Hyperlocomotive and Discriminative Stimulus Effects of Cocaine Are Under the Control of Serotonin2C (5-HT2C) Receptors in Rat Prefrontal Cortex
The data indicate that the PFC is a brain site at which the 5-HT2CR exerts an inhibitory control over the hyperactive and discriminative stimulus effects of cocaine known to be dependent upon activation of the DA mesoaccumbens circuit.
Effect of serotonin (5-HT)1B receptor ligands on cocaine sensitization in rats.
The results indicate that 5-HT1B receptors are involved in neither the development nor the expression of sensitization to cocaine-induced locomotor hyperactivity, and that repeated administration of cocaine leads to an increased functional reactivity of these receptors.
Effects of the 5-HT2C/2B Antagonist SB 206553 on Hyperactivity Induced by Cocaine
Discriminative stimulus properties of the serotonin agonist MK 212
The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5- HT agonists is difficult to explain.