1. Home
  2. Knowledge Base
  3. References
  4. Diacylglycerol lipase-α expression increases in the coeruleo-cortical pathway in dopamine-β-hydroxylase knockout mice as well as rats treated with DSP-4

Diacylglycerol lipase-α expression increases in the coeruleo-cortical pathway in dopamine-β-hydroxylase knockout mice as well as rats treated with DSP-4

Urquhart M, Reyes BAS, Thomas SA, Mackie K, Van Bockstaele EJ (2016) Diacylglycerol lipase-α expression increases in the coeruleo-cortical pathway in dopamine-β-hydroxylase knockout mice as well as rats treated with DSP-4. Neuroscience 2016 Abstracts 77.09 / AAA24. Society for Neuroscience, San Diego, CA.

Summary: Endocannabinoids are involved in the regulation of many physiological processes including behavioral responses to stress. Endocannabinoids modulate norepinephrine (NE) signaling primarily via involvement of CB1 cannabinoid receptors (CB1r). Our previous studies have shown that acute and repeated administration of a CB1r agonist increases multiple indices of noradrenergic activity involving the locus coeruleus (LC)-frontal cortex (FC) pathway. Diacylglycerol lipase-α (DGL-α), a key enzyme in the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) is localized to both the FC and the LC. Using electron microscopy, we have recently shown that in the rat FC DGL-α is localized in postsynaptic profiles that are targeted by dopamine-β-hydroxylase (DβH), the enzyme that converts dopamine to norepinephrine and represents a marker of noradrenergic neurons (Hartman et al., 1972). In this study, we also described interactions between DGL-α, CB1r and DβH in the FC using confocal microscopy. In the present study, we investigated expression levels of DGL-α under two conditions of NE deletion: in a rat model using a systemic injection of saporin conjugated with antibody against DβH (DSP-4) and in a genetically engineered mouse that lacked the enzyme DβH (DβH-knockout, KO). We compared expression levels of DGL-α to either control rats or wild type (WT) mice using Western blot analysis. Protein extracts from micropunches of FC and LC were obtained and probed for DGL-α. Results showed that DGL-α expression was significantly increased in FC (P < 0.05) of both DSP-4 treated rats and DβHKO mice when compared to WT mice. DGL-α expression was also significantly increased in the LC (P < 0.05) of DβHKO when compared to WT mice. These data add to the accumulating evidence that dysregulation of NE transmission results in significant adaptations in the brain endocannabinoid system.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Browse Articles

Need Support?

Can't find what you're looking for? Contact us, we're here to help!