Serotonergic hallucinogens differentially modify gamma and high frequency oscillations in the rat nucleus accumbens

• Published in: Psychopharmacology Vol. 228; no. 2; pp. 271 - 282
• Main Authors: Goda, Sailaja A., Piasecka, Joanna, Olszewski, Maciej, Kasicki, Stefan, Hunt, Mark J.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.07.2013; Springer; Springer Nature B.V
• Subjects: Amphetamines - administration & dosage; Amphetamines - pharmacology; Animals; Biomedical and Life Sciences; Biomedicine; Brain; Bridged Bicyclo Compounds - administration & dosage; Bridged Bicyclo Compounds - pharmacology; Dosage and administration; Dose-Response Relationship, Drug; Electric properties; Hallucinogenic drugs; Hallucinogens; Hallucinogens - administration & dosage; Hallucinogens - pharmacology; Health aspects; Injections, Intraperitoneal; Ketamine - pharmacology; Lysergic Acid Diethylamide - administration & dosage; Lysergic Acid Diethylamide - pharmacology; Male; Methylamines - administration & dosage; Methylamines - pharmacology; Neurosciences; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Original Investigation; Pharmacology/Toxicology; Physiological aspects; Piperazines - administration & dosage; Piperazines - pharmacology; Psychiatry; Psychopharmacology; Pyrazines - administration & dosage; Pyrazines - pharmacology; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT2A - drug effects; Receptor, Serotonin, 5-HT2A - metabolism; Rodents; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - administration & dosage; Serotonin Receptor Agonists - pharmacology; Poland; High frequency oscillations; Gamma; Accumbens; Rat; Local field potentials; Serotonin receptor; Lysergic acid diethylamide; Hallucinogens
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-013-3057-1

Rationale The nucleus accumbens (NAc) is a site critical for the actions of many drugs of abuse. Psychoactive compounds, such as N -methyl- d -aspartate receptor (NMDAR) antagonists, modify gamma (40-90) and high frequency oscillations (HFO, 130–180 Hz) in local field potentials (LFPs) recorded in the NAc. Lysergic acid diethylamide (LSD) and 2,5-dimethoxy-4-iodoamphetamine (DOI) are serotonergic hallucinogens and activation of 5HT 2A receptors likely underlies their hallucinogenic effects. Whether these compounds can also modulate LFP oscillations in the NAc is unclear. Objective This study aims to examine the effect of serotonergic hallucinogens on gamma and HFO recorded in the NAc and to test whether 5HT 2A receptors mediate the effects observed. Methods LFPs were recorded from the NAc of freely moving rats. Drugs were administered intraperitoneally. Results LSD (0.03–0.3 mg/kg) and DOI (0.5–2.0 mg/kg) increased the power and reduced the frequency of HFO. In contrast, the hallucinogens produced a robust reduction in the power of low (40–60 Hz), but not high gamma oscillations (70–90 Hz). MDL 11939 (1.0 mg/kg), a 5HT 2A receptor antagonist, fully reversed the changes induced by DOI on HFO but only partially for the low gamma band. Equivalent increases in HFO power were observed after TCB-2 (5HT 2A receptor agonist, 0.1–1.5 mg/kg), but not CP 809101 (5H 2C receptor agonist, 0.1–3 mg/kg). Notably, hallucinogen-induced increases in HFO power were smaller than those produced by ketamine (25 mg/kg). Conclusions Serotonergic hallucinogen-induced changes in HFO and gamma are mediated, at least in part, by stimulation of 5HT 2A receptors. Comparison of the oscillatory changes produced by serotonergic hallucinogens and NMDAR antagonists are also discussed.