title: Dopamine receptor blockade modulates the rewarding and aversive properties of nicotine via dissociable neuronal activity patterns in the nucleus accumbens.
abstract: The mesolimbic pathway comprising the ventral tegmental area (VTA) and projection terminals in the nucleus accumbens (NAc) has been identified as a critical neural system involved in processing both the rewarding and aversive behavioral effects of nicotine. Transmission through dopamine (DA) receptors functionally modulates these effects directly within the NAc. Nevertheless, the neuronal mechanisms within the NAc responsible for these bivalent behavioral effects are presently not known. Using an unbiased conditioned place preference procedure combined with in vivo neuronal recordings, we examined the effects of nicotine reward and aversion conditioning on intra-NAc neuronal sub-population activity patterns. We report that intra-VTA doses of nicotine that differentially produce rewarding or aversive behavioral effects produce opposite effects on sub-populations of fast-spiking interneurons (FSIs) or medium spiny neurons (MSNs) within the shell region of the NAc (NAshell). Thus, while the rewarding effects of intra-VTA nicotine were associated with inhibition of FSI and activation of MSNs, the aversive effects of nicotine produced the opposite pattern of NAshell neuronal population activity. Blockade of DA transmission with a broad-spectrum DA receptor antagonist, α-flupenthixol, strongly inhibited the spontaneous activity of NAshell FSIs, and reversed the conditioning properties of intra-VTA nicotine, switching nicotine-conditioned responses from aversive to rewarding. Remarkably, DA receptor blockade switched intra-NAshell neuronal population activity from an aversion to a reward pattern, concomitant with the observed switch in behavioral conditioning effects.
authors.affiliation: Department of Anatomy and Cell Biology, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Ninglei
authors.initials: N
authors.lastname: Sun
authors.affiliation: 1] Department of Anatomy and Cell Biology, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada [2] Department of Psychiatry, The Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada [3] Department of Psychology, The Schulich School of Medicine and 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; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005475:Flupenthixol / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology
chemical_list: D018492:Dopamine Antagonists; D018722:Nicotinic Agonists; D011954:Receptors, Dopamine; D009538:Nicotine; D005475:Flupenthixol