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 language | English (US) |
|---|---|
| Pages (from-to) | 745-756 |
| Number of pages | 12 |
| Journal | Pharmacology Biochemistry and Behavior |
| Volume | 71 |
| Issue number | 4 |
| DOIs | |
| State | Published - 2002 |
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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
Serotonin 5-HT2C receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine. / Filip, Malgorzata; Cunningham, Kathryn.
In: Pharmacology Biochemistry and Behavior, Vol. 71, No. 4, 2002, p. 745-756.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serotonin 5-HT2C receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine
AU - Filip, Malgorzata
AU - Cunningham, Kathryn
PY - 2002
Y1 - 2002
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.
KW - 5-HT receptors
KW - Behavior
KW - Cocaine
KW - Drug discrimination
KW - MK 212
KW - RO 60-0175
KW - RS 102221
KW - Serotonin
UR - http://www.scopus.com/inward/record.url?scp=0036119208&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036119208&partnerID=8YFLogxK
U2 - 10.1016/S0091-3057(01)00741-9
DO - 10.1016/S0091-3057(01)00741-9
M3 - Article
VL - 71
SP - 745
EP - 756
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
SN - 0091-3057
IS - 4
ER -