title: The alpha2 adrenergic receptor antagonist idazoxan, but not the serotonin-2A receptor antagonist M100907, partially attenuated reward deficits associated with nicotine, but not amphetamine, withdrawal in rats.
abstract: Based on phenomenological similarities between anhedonia (reward deficits) associated with drug withdrawal and the negative symptoms of schizophrenia, we showed previously that the atypical antipsychotic clozapine attenuated reward deficits associated with psychostimulant withdrawal. Antagonism of alpha(2) adrenergic and 5-HT(2A) receptors may contribute to these effects of clozapine. We investigated here whether blockade of alpha(2) or 5-HT(2A) receptors by idazoxan and M100907, respectively, would reverse anhedonic aspects of psychostimulant withdrawal. Idazoxan treatment facilitated recovery from spontaneous nicotine, but not amphetamine, withdrawal by attenuating reward deficits and increase the number of somatic signs. Thus, alpha(2) adrenoceptor blockade may have beneficial effects against nicotine withdrawal and may be involved in the effects of clozapine previously observed. M100907 worsened the anhedonia associated with nicotine and amphetamine withdrawal, suggesting that monotherapy with M100907 may exacerbate the expression of the negative symptoms of schizophrenia or nicotine withdrawal symptoms in people, including schizophrenia patients, attempting to quit smoking.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093-0603, USA. ssemenova@ucsd.edu
authors.forename: Svetlana
authors.initials: S
authors.lastname: Semenova
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000661:Amphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000008:administration & dosage / Q000494:pharmacology; D004567:Electrodes, Implanted; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000009:adverse effects; D019329:Idazoxan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D010880:Piperidines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism; D012201:Reward; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D058669:Adrenergic alpha-2 Receptor Antagonists; D005464:Fluorobenzenes; D005731:Ganglionic Stimulants; D010880:Piperidines; D011978:Receptors, Nicotinic; D012702:Serotonin Antagonists; D004079:Dihydro-beta-Erythroidine; D009538:Nicotine; D000661:Amphetamine; C079049:volinanserin; D019329:Idazoxan