5-Hydroxytryptamine (serotonin)2A receptors in rat anterior cingulate cortex mediate the discriminative stimulus properties of d-lysergic acid diethylamide.
Paul J Gresch, Robert J. Barrett, Elaine Sanders‐bush, Randy L Smith
Journal of Pharmacology and Experimental Therapeutics February 2007 DOI: 10.1124/jpet.106.112946 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study (drug discrimination with intracerebral microinjections) Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | LSD M100907 |
| Dose | LSD: 0.085 mg/kg s.c. (systemic training), 0.1875, 0.375, 0.75 microg/side (intra-ACC); M100907: 0.4 mg/kg (systemic), 0.5 microg/microl/side (intra-ACC) |
| Measures | drug discrimination (percent drug lever responding) |
| Topics | LSD Serotonin |
| Key findings | LSD infused into the anterior cingulate cortex dose-dependently substituted for systemically administered LSD, with complete substitution at 0.75 microg/side (89% correct). The 5-HT2A receptor antagonist M100907 blocked the discriminative cue of intra-ACC LSD and also blocked the stimulus effects of systemic LSD when infused locally, indicating that ACC 5-HT2A receptors mediate LSD's discriminative stimulus. |
Abstract
d-Lysergic acid diethylamide (LSD), an indoleamine hallucinogen, produces profound alterations in mood, thought, and perception in humans. The brain site(s) that mediates the effects of LSD is currently unknown. In this study, we combine the drug discrimination paradigm with intracerebral microinjections to investigate the anatomical localization of the discriminative stimulus of LSD in rats. Based on our previous findings, we targeted the anterior cingulate cortex (ACC) to test its involvement in mediating the discriminative stimulus properties of LSD. Rats were trained to discriminate systemically administered LSD (0.085 mg/kg s.c.) from saline. Following acquisition of the discrimination, bilateral cannulae were implanted into the ACC (AP, +1.2 mm; ML, +/-1.0 mm; DV, -2.0 mm relative to bregma). Rats were tested for their ability to discriminate varying doses of locally infused LSD (0.1875, 0.375, and 0.75 microg/side) or artificial cerebrospinal fluid (n = 3-7). LSD locally infused into ACC dose-dependently substituted for systemically administered LSD, with 0.75 microg/side LSD substituting completely (89% correct). Systemic administration of the selective 5-hydroxytryptamine (serotonin) (5-HT)(2A) receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907; 0.4 mg/kg) blocked the discriminative cue of LSD (0.375 microg/side) infused into ACC (from 68 to 16% drug lever responding). Furthermore, M100907 (0.5 microg/microl/side) locally infused into ACC completely blocked the stimulus effects of systemic LSD (0.04 mg/kg; from 80 to 12% on the LSD lever). Taken together, these data indicate that 5-HT(2A) receptors in the ACC are a primary target mediating the discriminative stimulus properties of LSD.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
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and 14 more in the library