Acquisition of and withdrawal from cocaine self-administration regulates 5-HT₁B mRNA expression in rat striatum

• Published in: Journal of neurochemistry Vol. 111; no. 1; pp. 217 - 227
• Main Authors: Neumaier, John F, McDevitt, Ross A, Polis, Ilham Y, Parsons, Loren H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.10.2009; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: 5-HT; 5‐HT6; Biochemistry; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cocaine; Drug addictions; escalation; forced abstinence; Fundamental and applied biological sciences. Psychology; Medical sciences; Neurology; Neurotransmitters; nucleus accumbens; Rodents; serotonin; Toxicology; Vertebrates: nervous system and sense organs; Rat; Serotonin; forced abstinence; Rodentia; Central nervous system; Projection; Basal ganglion; Corpus striatum; Serotonine receptor; Encephalon; Nucleus accumbens; Vertebrata; Mammalia; Neuron; Treatment; Addiction; escalation; Animal; 5-HT1B serotonin receptor; Neurotransmitter; 5-HT; Subtype
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06313.x

This study investigated how different stages of cocaine self-administration in rats affect the expression of two serotonin receptors in dorsal and ventral striatum, the 5-HT₁B and 5-HT₆ subtypes, which have both been implicated in mediating some aspects of cocaine-related behaviors. In the first experiment, rats were trained to work for saccharin (oral) or cocaine (i.v.) reinforcers. We found that continuous access to cocaine for 23 days did not change the level of 5-HT₁B mRNA expression compared to control animals receiving saccharin. However, a single cocaine session, given either by self-administration or non-contingently, increased 5-HT₁B mRNA in dorsal striatum, whereas forced abstinence for two weeks after cocaine reduced 5-HT₁B mRNA expression in the same subregion. 5-HT₆ mRNA was not changed by any of these treatments. A follow-up experiment investigated the effects of limited versus extended access to cocaine as well as forced abstinence, and we found that 14 days of forced abstinence significantly reduced 5-HT₁B mRNA throughout the dorsal and ventral striatum compared to no withdrawal. These results suggest that the influence of 5-HT₁B receptors in striatal projection neurons may be increased during cocaine acquisition and reduced after forced abstinence and may therefore be targets for pharmacological intervention in addiction.