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

Abstract

RationaleThe 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 5HT2A receptors likely underlies their hallucinogenic effects. Whether these compounds can also modulate LFP oscillations in the NAc is unclear.ObjectiveThis study aims to examine the effect of serotonergic hallucinogens on gamma and HFO recorded in the NAc and to test whether 5HT2A receptors mediate the effects observed.MethodsLFPs were recorded from the NAc of freely moving rats. Drugs were administered intraperitoneally.ResultsLSD (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 5HT2A 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 (5HT2A receptor agonist, 0.1–1.5 mg/kg), but not CP 809101 (5H2C receptor agonist, 0.1–3 mg/kg). Notably, hallucinogen-induced increases in HFO power were smaller than those produced by ketamine (25 mg/kg).ConclusionsSerotonergic hallucinogen-induced changes in HFO and gamma are mediated, at least in part, by stimulation of 5HT2A receptors. Comparison of the oscillatory changes produced by serotonergic hallucinogens and NMDAR antagonists are also discussed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00213-013-3057-1) contains supplementary material, which is available to authorized users.

Ventral striatal gamma oscillations are highly variable from trial to trial, and are dominated by behavioural state, and only weakly influenced by outcome value

“…Initial reports of vStr oscillations in behaving rats suggested that low-gamma (~50 Hz) and high-gamma (~80 Hz) power were differentially modulated upon approach to and receipt of reward (Berke, 2009;van der Meer & Redish, 2009;Howe et al, 2011). The relationship between aspects of reward processing and vStr gamma power is further substantiated by the apparent influence of dopaminergic and cannabinoid drugs on vStr gamma power (Berke, 2009;Morra et al, 2012;Goda et al, 2013).…”

Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations

“…Nevertheless, the impact of serotonergic hallucinogens on neuronal oscillations, and particularly the association of these oscillations with identifiable conscious states, is unclear. Initial animal studies performed with the hallucinogenic serotonin (5-HT) 2A/2C agonist, 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI), reported a DOI-induced reduction in delta (0.3-4 Hz) and gamma (30-80 Hz) oscillations in the prefrontal areas of the brain (Celada et al 2008;Puig et al 2010), in addition to a trend toward an increase in higher frequency (70-90 Hz) oscillations in subcortical structures (Goda et al 2013). In humans, oscillations decreased across a broad frequency range (up to 20 Hz) during eyes closed resting state after the administration of ayahuasca, a plant brew containing N,N-dimethyltryptamine (DMT), another naturally occurring serotonergic hallucinogen (Riba et al 2002;Riba et al 2004).…”

Brain Rhythms Connect Impaired Inhibition to Altered Cognition in Schizophrenia

“…Key to this multilevel analysis are temporal structures in the brain, including brain rhythms [2, 24]. Rhythmic alterations occur in schizophrenia and its animal models, accompany all neurotransmitter system manipulations that produce psychotic-like behavior [5, 25–29], and are candidate endophenotypes of the disease [30]. Rhythms are believed to play a key role in coordinating the activity of neuronal populations across multiple spatial and temporal scales [31–34], and are known to be associated with a wide range of cognitive and perceptual processes [35, 36].…”