Research in my lab is aimed at understanding the physiological function of the endogenous cannabinoid system with a particular emphasis on normal motivated behaviors as well as its potential therapeutic role in pathological states such as addiction.
Endogenous cannabinoids such as arachidonoylethanolamide (anandamide from the sanskrit word "ananda" meaning bliss) and 2-arachidonoylglycerol (2-AG) and their binding to central cannabinoid receptors (CB1) in the brain and spinal cord make up this recently described signaling system. These molecules have been involved in a wide spectrum of physiological states ranging from reinforcement processing to pain perception and executive function.
Our research employs state-of-the-art electrophysiological (ensemble recordings) and electrochemical (fast-scan cyclic voltammetry) techniques to extract neurobiological correlates of key aspects of behavior in real-time. We have also implemented the use of a microsensor that can simultaneously record extracellular single-unit activity and neurotransmitter release. These techniques are used in conjunction with pharmacological tools such as systemic administration, microinjection and iontophoresis to examine how endogenous cannabinoids modulate the encoding of motivated behavior.
We are specifically interested in the dopaminergic projection from the ventral tegmental area to the nucleus accumbens. Dopaminergic neurons burst fire in response to rewards and play a key role in the prediction of the availability of reward. We have shown that exogenous cannabinoids potently modulate the activity of dopaminergic neurons, in particular their ability to burst fire and to produce transient increases in dopamine concentration in the nucleus accumbens, suggesting that endogenous cannabinoids are indeed important mediators of reward encoding in behaving animals. Thus, understanding the interactions between endogenous cannabinoid and dopaminergic signaling in the nucleus accumbens during reward-related behavior is likely to yield unprecedented insight on the pathogenesis of disorders of motivation such as addiction.
Loewinger GC, Oleson EB and Cheer JF. (2013) Using dopamine research to generate rational cannabinoid drug policy. Drug Testing and Analysis 5: 22-26
Oleson EB, Gentry RN, Chioma VC, Cheer JF. (2012) Subsecond dopamine release in the nucleus accumbens predicts conditioned punishment and its successful avoidance. Journal of Neuroscience, 32: 14804-14808
Lee AM, Oleson EB, Diergaarde L, Cheer JF* and Pattij T*. (2012) Cannabinoids and value-based decision making: Implications for neurodegenerative disorders. Basal Ganglia 2: 131-138. Invited Review, * equal contribution
Oleson EB, Cheer JF. (2012) Paradoxical effects of the endocannabinoid uptake inhibitor VDM11 on accumbal neural encoding of reward predictive cues. Synapse. 66: 984-988
Hernandez G and Cheer JF. (2012) Effect of CB1 Receptor Blockade on Food-Reinforced Responding and Associated Nucleus AccumbensNeuronal Activity in Rats. Journal of Neuroscience. 32: 11467-11477.
Oleson EB and Cheer JF. (2012) A brain on cannabinoids: the role of dopamine release in reward seeking. Cold Spring Harbor Perspectives in Medicine. 1;2(8)
Loewinger G; Beckert MV; Tejeda H and Cheer JF. (2012) Enduring methamphetamine-induced dopaminergic effects in the nucleus accumbens are exacerbated by reward associated cues and attenuated by CB1 receptor antagonism. Neuropharmacology 62: 2191-2200.
Morra JT; Glick SD and Cheer JF. (2012) Cannabinoid receptors mediate methamphetamine induction of gamma oscillations in the nucleus accumbens. Neuropharmacology 63: 565-574.
Cachope R; Mateo Y; Mathur BN; Irving J; Wang HL; Morales M; Lovinger DM and Cheer JF. (2012) Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing. Cell Reports 2: 33-41.
Oleson EB, Beckert MV, Morra JT, Lansink CS, Cachope R, Abdullah R, Loriaux Al, Schetters D, Pattij T, Roitman MF, Lichtman AH and Cheer JF. (2012) Endocannabinoids shape accumbal encoding of cue-motivated behavior via CB1 receptor activation in the ventral tegmentum. Neuron 73: 360-373.
Mazei-Robison MS, Koo JW, Lansink CS, Han MH, Robison AJ, Krishnan V, Kim S, Siuta MA, Galli A, Neve RL, Snyder SH, Cheer JF, Russo S and EJ. Nestler. (2011) Morphine-induced changes in dopamine ventral tegmental area neuronal morphology are dependent on mTOR signaling and neuronal activity. Neuron 72: 977-990.
Hernandez G, Bernstein D, Schoenbaum G and Cheer JF. (2011) Contrasting Effects of Lithium Chloride and CB1 Receptor Blockade on Enduring Changes in the Valuation of Reward. Frontiers in Behavioral Neuroscience. 5: 53
Hernandez G and Cheer JF. (2011) Extinction learning of rewards in the rat: is there a role for CB1 receptors? Psychopharmacology (Berl). 217: 189-197
Trujillo-Pisanty I, Hernandez G, Moreau-Debord I, Cossette MP, Conover K, Cheer JF and Shizgal P. (2011) Cannabinoid receptor blockade reduces the opportunity cost at which rats maintain operant performance for rewarding brain stimulation. Journal of Neuroscience. 31: 5426-5435
Morra JT, Glick SD and Cheer JF. (2010) Neural encoding of psychomotor activation in the nucleus accumbens core, but not the shell, requires cannabinoid receptor signaling. Journal of Neuroscience. 30: 5102-5107
Mason R and Cheer JF. (2009) Cannabinoid receptor activation reverses kainate-induced synchronized population burst firing in rat hippocampus. Frontiers in Integrative Neuroscience. 3:13.
Villanueva A; Yilmaz MS; Millington WR; Cutrera RA; Stouffer DG; Parsons LH; Cheer JF* and Feleder C*. (2009) Central Cannabinoid-1 Receptor Antagonist Administration Prevents Endotoxic Hypotension Affecting Norepinephrine Release in the Preoptic Anterior Hypothalamic Area. Shock. 32: 514-620. (* Equal contribution)
Cheer JF; Heien MLAV; Ariansen JL; Aragona BJ, Carelli RM and Wightman RM. (2007) Coordinated accumbal dopamine release and neural activity drive goal-directed behavior. Neuron 54: 237-244
Cheer JF; Wassum KM; Sombers LA; Heien MLAV; Ariansen JL; Aragona BJ; Phillips PEM and Wightman RM (2007) Phasic dopamine release evoked by abused substances requires cannabinoid receptor activation. Journal of Neuroscience 27: 791-795
Cheer JF*; Heien MLAV*; Garris PA; Carelli RM and Wightman RM (2005) Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: implications for intracranial self-stimulation. Proceedings of the National Academy of Sciences of the United States of America 102: 19150-19155 * These authors contributed equally
Heien MLAV; Khan AS; Ariansen JL; Cheer JF; Phillips PEM; Wassum KM and Wightman RM (2005) Principal component regression resolves dopamine fluctuations in the brain of behaving rats revealed from in vivo voltammetry. Proceedings of the National Academy of Sciences of the United States of America 102: 10023-10028
Cheer JF; Wassum K; Heien MLAV; Phillips PEM and Wightman RM (2004) Cannabinoids enhance subsecond dopamine release in the nucleus accumbens of awake rats. Journal of Neuroscience 24: 4393-4400