title: Nicotine potentiation of brain stimulation reward reversed by DH beta E and SCH 23390, but not by eticlopride, LY 314582 or MPEP in rats.
abstract: BACKGROUND
  Systemic nicotine administration increases dopamine and glutamate levels in reward-related brain areas. Nicotine-induced increases of dopamine in the nucleus accumbens are in part mediated by glutamatergic projections to the ventral tegmental area dopamine neurons.
  
  
  OBJECTIVE
  To assess the effects of actions at acetylcholine, dopamine, presynaptic (mGluR(2/3)) and postsynaptic (mGluR(5)) metabotropic glutamate receptors (mGluRs) on the potentiation of brain stimulation reward induced by systemically administered nicotine (0.125-0.5 mg/kg; free base) in rats.
  
  
  METHODS
  A discrete-trial current-threshold s stimulation reward procedure (electrodes placed in the posterior lateral hypothalamus) was used to assess the effects of DH beta E (0.5-5 mg/kg), an acetylcholine nicotinic receptor antagonist, SCH 23390 (1.25-5 microg/kg), a dopamine D(1) receptor antagonist, eticlopride (2.5-20 microg/kg), a dopamine D(2) receptor antagonist, LY 314582 (1-20 mg/kg), an mGluR(2/3) agonist, and MPEP (1-9 mg/kg), an mGluR(5) antagonist, on the reward potentiating effects of nicotine (0.25 mg/kg).
  
  
  RESULTS
  DH beta E had no effect on reward thresholds when administered alone, but dose-dependently reversed the nicotine-induced potentiation of brain stimulation reward. SCH 23390 (5 microg/kg) elevated thresholds when administered alone, and reversed the nicotine-induced potentiation of brain stimulation reward even at a dose (2.5 microg/kg) that had no effect on reward thresholds. Eticlopride (10-20 microg/kg), LY 314582 (10-20 mg/kg) and MPEP (9 mg/kg) elevated thresholds when administered alone but had no effect on the nicotine-induced potentiation of brain stimulation reward.
  
  
  CONCLUSIONS
  These results indicate that nicotinic and dopamine D(1) receptors are involved in the nicotine-induced potentiation of brain stimulation reward, while actions at dopamine D(2), mGlu(2/3) and mGlu(5) receptors did not modulate this effect of nicotine.
authors.affiliation: Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Harrison
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gasparini
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D001921:Brain / Q000502:physiology*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D011978:Receptors, Nicotinic / Q000187:drug effects; D012201:Reward; D012457:Salicylamides / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D001643:Bridged Bicyclo Compounds; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D017447:Receptors, Dopamine D1; D018094:Receptors, Metabotropic Glutamate; D011978:Receptors, Nicotinic; D012457:Salicylamides; C108822:metabotropic glutamate receptor 2; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; C121465:6-methyl-2-(phenylethynyl)pyridine; C045989:eticlopride; C104753:eglumetad