title: Hippocampal cannabinoid transmission modulates dopamine neuron activity: impact on rewarding memory formation and social interaction.
abstract: Disturbances in cannabinoid type 1 receptor (CB1R) signaling have been linked to emotional and cognitive deficits characterizing neuropsychiatric disorders, including schizophrenia. Thus, there is growing interest in characterizing the relationship between cannabinoid transmission, emotional processing, and dopamine (DA)-dependent behavioral deficits. The CB1R is highly expressed in the mammalian nervous system, particularly in the hippocampus. Activation of the ventral hippocampal subregion (vHipp) is known to increase both the activity of DAergic neurons located in the ventral tegmental area (VTA) and DA levels in reward-related brain regions, particularly the nucleus accumbens (NAc). However, the possible functional relationship between hippocampal CB1R transmission and VTA DA neuronal activity is not currently understood. In this study, using in vivo neuronal recordings in rats, we demonstrate that activation of CB1R in the vHipp strongly increases VTA DA neuronal firing and bursting activity, while simultaneously decreasing the activity of VTA non-DA neurons. Furthermore, using a conditioned place preference procedure and a social interaction test, we report that intra-vHipp CB1R activation potentiates the reward salience of normally sub-threshold conditioning doses of opiates and induces deficits in natural sociability and social recognition behaviors. Finally, these behavioral effects were prevented by directly blocking NAc DAergic transmission. Collectively, these findings identify hippocampal CB1R transmission as a critical modulator of the mesolimbic DA pathway and in the processing of reward and social-related behavioral phenomena.
authors.affiliation: Department of Anatomy and Cell Biology, The Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Loureiro
authors.affiliation: Department of Anatomy and Cell Biology, The Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Justine
authors.initials: J
authors.lastname: Renard
authors.affiliation: Department of Anatomy and Cell Biology, The Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Jordan
authors.initials: J
authors.lastname: Zunder
authors.affiliation: 1] Department of Anatomy and Cell Biology, The Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada [2] Department of Psychiatry, The Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada [3] Department of Psychology, The Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Laviolette
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007398:Interpersonal Relations; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D011954:Receptors, Dopamine; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: C543264:Cnr1 protein, rat; D043884:Receptor, Cannabinoid, CB1; D011954:Receptors, Dopamine