Cannabinoid receptors mediate methamphetamine induction of high frequency gamma oscillations in the nucleus accumbens

Abstract

Patients suffering from amphetamine---induced psychosis display repetitive behaviors, partially alleviated by antipsychotics, which are reminiscent of rodent stereotypies. Due to recent evidence implicating endocannabinoid involvement in brain disorders, including psychosis, we studied the effects of endocannabinoid signaling on neuronal oscillations of rats exhibiting methamphetamine stereotypy. Neuronal network oscillations were recorded with multiple single electrode arrays aimed at the nucleus accumbens of freely moving rats. During the experiments, animals were dosed intravenously with the CB1 receptor antagonist rimonabant (0.3 mg/kg) or vehicle followed by an ascending dose regimen of methamphetamine (0.01, 0.1, 1, and 3 mg/kg; cumulative dosing). The effects of drug administration on stereotypy and local gamma oscillations were evaluated. Methamphetamine treatment significantly increased high frequency gamma oscillations (~ 80 Hz). Entrainment of a subpopulation of nucleus accumbens neurons to high frequency gamma was associated with stereotypy encoding in putative fast-spiking interneurons, but not in putative medium spiny neurons. The observed ability of methamphetamine to induce both stereotypy and high frequency gamma power was potently disrupted following CB1 receptor blockade. The present data suggest that CB1 receptor-dependent mechanisms are recruited by methamphetamine to modify striatal interneuron oscillations that accompany changes in psychomotor state, further supporting the link between endocannabinoids and schizophrenia spectrum disorders.

Effect of CB1 Receptor Blockade on Food-Reinforced Responding and Associated Nucleus Accumbens Neuronal Activity in Rats

“…LFPs can be the product of electrical field changes produced in other brain areas rather than the one in which the electrodes are located (Berke 2005). However, and in accordance with prior studies, our data shows that LFPs recorded from the NAc are in part controlled by FSIs (Berke, 2005; van der Meer and Redish, 2009; Kalenscher et al, 2010, Morra et al, 2012). “Gamma-80” has been previously linked to reward delivery (Berke, 2004; van der Meer and Redish, 2009); whereas “gamma-50” has been linked among other functions to movement initiation (Masimore et al, 2004; for a review see van der Meer et al, 2010).…”

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

“…However, he observed decreased low gamma was also associated with an increase in the power of high gamma. A very recent study examining the effect of methamphetamine on accumbal gamma also demonstrated an increase in the power of high gamma, but reported no significant effects on the power of low gamma (Morra et al 2012). In contrast to psychostimulants, serotonergic hallucinogens did not increase the absolute power of high gamma in the NAc indicating fundamental differences between these drugs.…”

“…Systemic injection of d -amphetamine and methamphetamine reduce the power of low gamma but increase high gamma power in the NAc of freely moving rats (Berke 2009; Morra et al 2012). Frequencies above the gamma range, known as high-frequency oscillations (130–180 Hz), also occur in the NAc of freely moving rats.…”

Slow Gamma Activity of Local Field Potentials (LFP) in the Freely Moving Rat Relates to Movement

“…There is also evidence in humans that not only motion itself but also perception of biological motion relates to gamma activity, in this case so-called high gamma frequencies (70 -100 Hz) [9]. High gamma oscillations (70 -94 Hz) have also been recorded from nucleus accumbens in rats during induction of stereotype behavior by methamphetamine [10]. In this case a relationship was detected between this high gamma activity and the cannabinoid receptor CB1.…”