Serotonin 5-HT2C receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine

Malgorzata Filip, Kathryn Cunningham

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The serotonin 5-HT2C receptor (5-HT2CR) is abundant in the nucleus accumbens (NAc) shell and is considered an important target for 5-HT to modulate the dopamine (DA) mesoaccumbens circuit, which plays a prominent role in the behavioral effects of cocaine. The present study analyzed the ability of intra-NAc shell infusions of the 5-HT2CR agonists, MK 212 and RO 60-0175, or the 5-HT2CR antagonist, RS 102221, to alter either spontaneous or cocaine-evoked activity as well as the discriminative stimulus properties of cocaine. In male Sprague-Dawley rats implanted with bilateral cannulae aimed at the NAc shell, locally injected MK 212 (0.05-0.5 μg/side) or RO 60-0175 (0.5-5 μg/side) did not alter spontaneous activity, but dose-dependently enhanced hyperactivity evoked by cocaine (10 mg/kg ip). In rats trained to discriminate cocaine (10 mg/kg ip) from saline (ip) in a two-lever, water-reinforced FR 20 task, intra-NAc microinfusion of MK 212 (0.05 μg/side) or RO 60-0175 (0.5 μg/side) evoked 37% or 48% cocaine lever responding, respectively. Both MK 212 (0.05 μg/side) and RO 60-0175 (0.5 μg/side) enhanced the discriminability of submaximal doses of cocaine (0.625-2.5 mg/kg). Moreover, intra-NAc infusion of RS 102221 (0.05-1.5 μg/side) dose-dependently attenuated the stimulus effects of cocaine. These data reinforce the hypothesis that 5-HT2CR plays a role in the regulatory neurochemistry of the NAc shell that is important to the full expression of the behaviors evoked by cocaine.

Original languageEnglish (US)
Pages (from-to)745-756
Number of pages12
JournalPharmacology Biochemistry and Behavior
Volume71
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Receptor, Serotonin, 5-HT2C
Nucleus Accumbens
Cocaine
Rats
Serotonin 5-HT2 Receptor Agonists
Serotonin 5-HT2 Receptor Antagonists
Neurochemistry
Aptitude
Sprague Dawley Rats
Dopamine
Serotonin

Keywords

  • 5-HT receptors
  • Behavior
  • Cocaine
  • Drug discrimination
  • MK 212
  • RO 60-0175
  • RS 102221
  • Serotonin

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

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title = "Serotonin 5-HT2C receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine",
abstract = "The serotonin 5-HT2C receptor (5-HT2CR) is abundant in the nucleus accumbens (NAc) shell and is considered an important target for 5-HT to modulate the dopamine (DA) mesoaccumbens circuit, which plays a prominent role in the behavioral effects of cocaine. The present study analyzed the ability of intra-NAc shell infusions of the 5-HT2CR agonists, MK 212 and RO 60-0175, or the 5-HT2CR antagonist, RS 102221, to alter either spontaneous or cocaine-evoked activity as well as the discriminative stimulus properties of cocaine. In male Sprague-Dawley rats implanted with bilateral cannulae aimed at the NAc shell, locally injected MK 212 (0.05-0.5 μg/side) or RO 60-0175 (0.5-5 μg/side) did not alter spontaneous activity, but dose-dependently enhanced hyperactivity evoked by cocaine (10 mg/kg ip). In rats trained to discriminate cocaine (10 mg/kg ip) from saline (ip) in a two-lever, water-reinforced FR 20 task, intra-NAc microinfusion of MK 212 (0.05 μg/side) or RO 60-0175 (0.5 μg/side) evoked 37{\%} or 48{\%} cocaine lever responding, respectively. Both MK 212 (0.05 μg/side) and RO 60-0175 (0.5 μg/side) enhanced the discriminability of submaximal doses of cocaine (0.625-2.5 mg/kg). Moreover, intra-NAc infusion of RS 102221 (0.05-1.5 μg/side) dose-dependently attenuated the stimulus effects of cocaine. These data reinforce the hypothesis that 5-HT2CR plays a role in the regulatory neurochemistry of the NAc shell that is important to the full expression of the behaviors evoked by cocaine.",
keywords = "5-HT receptors, Behavior, Cocaine, Drug discrimination, MK 212, RO 60-0175, RS 102221, Serotonin",
author = "Malgorzata Filip and Kathryn Cunningham",
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N2 - The serotonin 5-HT2C receptor (5-HT2CR) is abundant in the nucleus accumbens (NAc) shell and is considered an important target for 5-HT to modulate the dopamine (DA) mesoaccumbens circuit, which plays a prominent role in the behavioral effects of cocaine. The present study analyzed the ability of intra-NAc shell infusions of the 5-HT2CR agonists, MK 212 and RO 60-0175, or the 5-HT2CR antagonist, RS 102221, to alter either spontaneous or cocaine-evoked activity as well as the discriminative stimulus properties of cocaine. In male Sprague-Dawley rats implanted with bilateral cannulae aimed at the NAc shell, locally injected MK 212 (0.05-0.5 μg/side) or RO 60-0175 (0.5-5 μg/side) did not alter spontaneous activity, but dose-dependently enhanced hyperactivity evoked by cocaine (10 mg/kg ip). In rats trained to discriminate cocaine (10 mg/kg ip) from saline (ip) in a two-lever, water-reinforced FR 20 task, intra-NAc microinfusion of MK 212 (0.05 μg/side) or RO 60-0175 (0.5 μg/side) evoked 37% or 48% cocaine lever responding, respectively. Both MK 212 (0.05 μg/side) and RO 60-0175 (0.5 μg/side) enhanced the discriminability of submaximal doses of cocaine (0.625-2.5 mg/kg). Moreover, intra-NAc infusion of RS 102221 (0.05-1.5 μg/side) dose-dependently attenuated the stimulus effects of cocaine. These data reinforce the hypothesis that 5-HT2CR plays a role in the regulatory neurochemistry of the NAc shell that is important to the full expression of the behaviors evoked by cocaine.

AB - The serotonin 5-HT2C receptor (5-HT2CR) is abundant in the nucleus accumbens (NAc) shell and is considered an important target for 5-HT to modulate the dopamine (DA) mesoaccumbens circuit, which plays a prominent role in the behavioral effects of cocaine. The present study analyzed the ability of intra-NAc shell infusions of the 5-HT2CR agonists, MK 212 and RO 60-0175, or the 5-HT2CR antagonist, RS 102221, to alter either spontaneous or cocaine-evoked activity as well as the discriminative stimulus properties of cocaine. In male Sprague-Dawley rats implanted with bilateral cannulae aimed at the NAc shell, locally injected MK 212 (0.05-0.5 μg/side) or RO 60-0175 (0.5-5 μg/side) did not alter spontaneous activity, but dose-dependently enhanced hyperactivity evoked by cocaine (10 mg/kg ip). In rats trained to discriminate cocaine (10 mg/kg ip) from saline (ip) in a two-lever, water-reinforced FR 20 task, intra-NAc microinfusion of MK 212 (0.05 μg/side) or RO 60-0175 (0.5 μg/side) evoked 37% or 48% cocaine lever responding, respectively. Both MK 212 (0.05 μg/side) and RO 60-0175 (0.5 μg/side) enhanced the discriminability of submaximal doses of cocaine (0.625-2.5 mg/kg). Moreover, intra-NAc infusion of RS 102221 (0.05-1.5 μg/side) dose-dependently attenuated the stimulus effects of cocaine. These data reinforce the hypothesis that 5-HT2CR plays a role in the regulatory neurochemistry of the NAc shell that is important to the full expression of the behaviors evoked by cocaine.

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