Components of the cannabinoid system in the dorsal periaqueductal gray are related to resting heart rate

Abstract

The present study was undertaken to examine whether variations in endocannabinoid signaling in the dorsal periaqueductal gray (dPAG) are associated with baseline autonomic nerve activity, heart rate, and blood pressure. Blood pressure was recorded telemetrically in rats, and heart rate and power spectral analysis of heart rate variability were determined. Natural variations from animal to animal provided a range of baseline values for analysis. Transcript levels of endocannabinoid signaling components in the dPAG were analyzed, and endocannabinoid content and catabolic enzyme activity were measured. Higher baseline heart rate was associated with increased anandamide content and with decreased activity of the anandamide-hydrolyzing enzyme and fatty acid amide hydrolase (FAAH), and it was negatively correlated with transcript levels of both FAAH and monoacylglycerol lipase (MAGL), a catabolic enzyme for 2-arachidonoylglycerol (2-AG). Autonomic tone and heart rate, but not blood pressure, were correlated to levels of FAAH mRNA. In accordance with these data, exogenous anandamide in the dPAG of anesthetized rats increased heart rate. These data indicate that in the dPAG, anandamide, a FAAH-regulated lipid, contributes to regulation of baseline heart rate through influences on autonomic outflow.

The effects of trauma on brain and body: A unifying role for the midbrain periaqueductal gray

“…Here, endocannabinoids are important regulators of the biological stress response, playing a neuromodulatory role in the inhibition of excitatory and inhibitory neurotransmitter release (for a review, see Hill et al, ; Micale & Drago, ). Not only have the effects of endocannabinoids been demonstrated following repeated stress, but endocannabinoids have been shown to impact the physiological components of the fight‐or‐flight response, including heart rate and baseline autonomic nerve activity (Dean, ; Dean, Hillard, Seagard, Hopp, & Hogan, ; for a review see, Hill et al, ; Lanius et al, ). Prior to endocannabinoid signaling, the periaqueductal gray is thought to receive projections from the hypothalamus and the limbic forebrain, including from several regions of the frontal neocortex and amygdala (Campos & Guimarães, ; Fogaça, Aguiar, Moreira, & Guimarães, ; Lisboa, Resstel, Aguiar, & Guimarães, ; for a review, see Fields, ).…”

“…These inputs provide the periaqueductal gray with threat information such that it gains capacity to initiate an active or a passive defensive response. During an active response, lateral periaqueductal gray projections to the ventral medulla initiate endocannabinoid‐mediated pain response (Benarroch, ; Dean et al, ; Lee et al, ; for a review, see Brooks & Tracey, ). In turn, these pain signals terminate at nociceptive relay neurons located in the dorsal horn laminae of the spinal cord to induce a pain‐relieving state (Walker, Huang, Strangman, Tsou, & Sanudo‐Pena, ; Wall, ; Willis & Coggeshall, ).…”

Role of endocannabinoids in the hippocampus and amygdala in emotional memory and plasticity

“…Activities of FAAH and MAGL were determined at a single concentration of substrate as described previously [25]. Membranes and cytosol were both harvested from homogenates of the tissues; FAAH activity was determined in the membrane fraction while MAGL activity was determined in the cytosolic fraction, in the presence of the FAAH inhibitor URB597 (1 µM) to block any residual FAAH activity in this fraction.…”

Functional Involvement of Human Periaqueductal Gray and Other Midbrain Nuclei in Cognitive Control

“…Our imaging protocol localized effects to different PAG columns, which are associated with distinct patterns of behavioral and autonomic responses (Carrive and Morgan, 2012). In particular, the ventrolateral PAG is associated with sympathetic inhibition (Johnson et al, 2004), whereas the dorsal PAG is associated with sympathetic activation (Dean et al, 2016). Thus, we investigated whether activity during cognitive demand engaged particular subregions of the PAG.…”