Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline
•Male and female rats had no differences during maintenance and extinction.•Both males and females showed reinstatement to the CAF+CUES condition.•Male rats, but not females, reinstated to the NIC+CUES condition.•Varenicline alone attenuated NIC+CUES reinstatement in males.•Combination varenicline a...
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| Veröffentlicht in: | Behavioural brain research 2016-07, Vol.308, p.46-52 |
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| creator | Swalve, Natashia Smethells, John R. Carroll, Marilyn E. |
| description | •Male and female rats had no differences during maintenance and extinction.•Both males and females showed reinstatement to the CAF+CUES condition.•Male rats, but not females, reinstated to the NIC+CUES condition.•Varenicline alone attenuated NIC+CUES reinstatement in males.•Combination varenicline and progesterone decreased NIC+CUES reinstatement in males.
Tobacco use is the largest cause of preventable mortality in the western world. Even after treatment, relapse rates for tobacco are high, and more effective pharmacological treatments are needed. Progesterone (PRO), a female hormone used in contraceptives, reduces stimulant use but its effects on tobacco addiction are unknown. Varenicline (VAR) is a commonly used medication that reduces tobacco use. The present study examined sex differences in the individual vs. combined effects of PRO and VAR on reinstatement of nicotine-seeking behavior in a rat model of relapse. Adult female and male Wistar rats self-administered nicotine (NIC, 0.03mg/kg/infusion) for 14days followed by 21days of extinction when no cues or drug were present. Rats were then divided into 4 treatment groups: control (VEH+SAL), PRO alone (PRO+SAL), VAR alone (VEH+VAR) and the combination (PRO+VAR). Reinstatement of nicotine-seeking behavior induced by priming injections of NIC or caffeine (CAF), presentation of cues (CUES), and the combination of drugs and cues (e.g. NIC+CUES, CAF+CUES) were tested after extinction. Male and female rats did not differ in self-administration of nicotine or extinction responding, and both showed elevated levels of responding to the CAF+CUES condition. However, males, but not females, reinstated active lever-pressing to the NIC+CUES condition, and that was attenuated by both VAR and VAR+PRO treatment. Thus, males were more sensitive to NIC+CUE-induced reinstatement than females, and VAR alone and VAR combined with PRO effectively reduced nicotine relapse. |
| doi_str_mv | 10.1016/j.bbr.2016.04.023 |
| format | Article |
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Tobacco use is the largest cause of preventable mortality in the western world. Even after treatment, relapse rates for tobacco are high, and more effective pharmacological treatments are needed. Progesterone (PRO), a female hormone used in contraceptives, reduces stimulant use but its effects on tobacco addiction are unknown. Varenicline (VAR) is a commonly used medication that reduces tobacco use. The present study examined sex differences in the individual vs. combined effects of PRO and VAR on reinstatement of nicotine-seeking behavior in a rat model of relapse. Adult female and male Wistar rats self-administered nicotine (NIC, 0.03mg/kg/infusion) for 14days followed by 21days of extinction when no cues or drug were present. Rats were then divided into 4 treatment groups: control (VEH+SAL), PRO alone (PRO+SAL), VAR alone (VEH+VAR) and the combination (PRO+VAR). Reinstatement of nicotine-seeking behavior induced by priming injections of NIC or caffeine (CAF), presentation of cues (CUES), and the combination of drugs and cues (e.g. NIC+CUES, CAF+CUES) were tested after extinction. Male and female rats did not differ in self-administration of nicotine or extinction responding, and both showed elevated levels of responding to the CAF+CUES condition. However, males, but not females, reinstated active lever-pressing to the NIC+CUES condition, and that was attenuated by both VAR and VAR+PRO treatment. Thus, males were more sensitive to NIC+CUE-induced reinstatement than females, and VAR alone and VAR combined with PRO effectively reduced nicotine relapse.</description><identifier>ISSN: 0166-4328</identifier><identifier>EISSN: 1872-7549</identifier><identifier>DOI: 10.1016/j.bbr.2016.04.023</identifier><identifier>PMID: 27091301</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Disease Models, Animal ; Drug Combinations ; Drug-Seeking Behavior - drug effects ; Extinction, Psychological - drug effects ; Female ; Male ; Nicotine ; Nicotine - adverse effects ; Nicotinic Agonists - pharmacology ; Progesterone - pharmacology ; Progestins - pharmacology ; Rats ; Rats, Wistar ; Reinforcement Schedule ; Reinstatement ; Self Administration ; Sex differences ; Sex Factors ; Smoking Cessation ; Varenicline - pharmacology</subject><ispartof>Behavioural brain research, 2016-07, Vol.308, p.46-52</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c484t-642584b95677bf7046ef6b1da1f57476afe8fa0d696ca07236571a2613ece2bd3</citedby><cites>FETCH-LOGICAL-c484t-642584b95677bf7046ef6b1da1f57476afe8fa0d696ca07236571a2613ece2bd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0166432816302248$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27091301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Swalve, Natashia</creatorcontrib><creatorcontrib>Smethells, John R.</creatorcontrib><creatorcontrib>Carroll, Marilyn E.</creatorcontrib><title>Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline</title><title>Behavioural brain research</title><addtitle>Behav Brain Res</addtitle><description>•Male and female rats had no differences during maintenance and extinction.•Both males and females showed reinstatement to the CAF+CUES condition.•Male rats, but not females, reinstated to the NIC+CUES condition.•Varenicline alone attenuated NIC+CUES reinstatement in males.•Combination varenicline and progesterone decreased NIC+CUES reinstatement in males.
Tobacco use is the largest cause of preventable mortality in the western world. Even after treatment, relapse rates for tobacco are high, and more effective pharmacological treatments are needed. Progesterone (PRO), a female hormone used in contraceptives, reduces stimulant use but its effects on tobacco addiction are unknown. Varenicline (VAR) is a commonly used medication that reduces tobacco use. The present study examined sex differences in the individual vs. combined effects of PRO and VAR on reinstatement of nicotine-seeking behavior in a rat model of relapse. Adult female and male Wistar rats self-administered nicotine (NIC, 0.03mg/kg/infusion) for 14days followed by 21days of extinction when no cues or drug were present. Rats were then divided into 4 treatment groups: control (VEH+SAL), PRO alone (PRO+SAL), VAR alone (VEH+VAR) and the combination (PRO+VAR). Reinstatement of nicotine-seeking behavior induced by priming injections of NIC or caffeine (CAF), presentation of cues (CUES), and the combination of drugs and cues (e.g. NIC+CUES, CAF+CUES) were tested after extinction. Male and female rats did not differ in self-administration of nicotine or extinction responding, and both showed elevated levels of responding to the CAF+CUES condition. However, males, but not females, reinstated active lever-pressing to the NIC+CUES condition, and that was attenuated by both VAR and VAR+PRO treatment. Thus, males were more sensitive to NIC+CUE-induced reinstatement than females, and VAR alone and VAR combined with PRO effectively reduced nicotine relapse.</description><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>Drug Combinations</subject><subject>Drug-Seeking Behavior - drug effects</subject><subject>Extinction, Psychological - drug effects</subject><subject>Female</subject><subject>Male</subject><subject>Nicotine</subject><subject>Nicotine - adverse effects</subject><subject>Nicotinic Agonists - pharmacology</subject><subject>Progesterone - pharmacology</subject><subject>Progestins - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reinforcement Schedule</subject><subject>Reinstatement</subject><subject>Self Administration</subject><subject>Sex differences</subject><subject>Sex Factors</subject><subject>Smoking Cessation</subject><subject>Varenicline - pharmacology</subject><issn>0166-4328</issn><issn>1872-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1vFSEUhomxsdfqD3BjWLqZERgGZmJiYhq_kiYu2q4JA4fKzQxcgbnRpf9cJrc2utEVJOc5L-fwIPSCkpYSKl7v22lKLavXlvCWsO4R2tFBskb2fHyMdrUgGt6x4Rw9zXlPCOGkp0_QOZNkpB2hO_TzGr5j652DBMFAxj5gXQqEVRcfA44OB29i8QFwAh9y0QUWCAVrVyBV3Pqjt6uesQ4Wm7hMFbW4JNBl4_IWcUjxDnLlY43ZuKOuz3kzV_YZOnN6zvD8_rxAtx_e31x-aq6-fPx8-e6qMXzgpRGc9QOfxl5IOTlJuAAnJmo1db3kUmgHg9PEilEYTSTrRC-pZoJ2YIBNtrtAb0-5h3VawJo6W9KzOiS_6PRDRe3V35Xgv6q7eFR8kJIxWQNe3Qek-G2t66jFZwPzrAPENSs6kEH0pNL_R-VIRsb7jleUnlCTYs4J3MNElKjNstqralltlhXhqlquPS__XOWh47fWCrw5AVA_9OghqWz85tf6BKYoG_0_4n8BtPm71A</recordid><startdate>20160715</startdate><enddate>20160715</enddate><creator>Swalve, Natashia</creator><creator>Smethells, John R.</creator><creator>Carroll, Marilyn E.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QG</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20160715</creationdate><title>Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline</title><author>Swalve, Natashia ; Smethells, John R. ; Carroll, Marilyn E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c484t-642584b95677bf7046ef6b1da1f57476afe8fa0d696ca07236571a2613ece2bd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Disease Models, Animal</topic><topic>Drug Combinations</topic><topic>Drug-Seeking Behavior - drug effects</topic><topic>Extinction, Psychological - drug effects</topic><topic>Female</topic><topic>Male</topic><topic>Nicotine</topic><topic>Nicotine - adverse effects</topic><topic>Nicotinic Agonists - pharmacology</topic><topic>Progesterone - pharmacology</topic><topic>Progestins - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reinforcement Schedule</topic><topic>Reinstatement</topic><topic>Self Administration</topic><topic>Sex differences</topic><topic>Sex Factors</topic><topic>Smoking Cessation</topic><topic>Varenicline - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Swalve, Natashia</creatorcontrib><creatorcontrib>Smethells, John R.</creatorcontrib><creatorcontrib>Carroll, Marilyn E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Animal Behavior Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Behavioural brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Swalve, Natashia</au><au>Smethells, John R.</au><au>Carroll, Marilyn E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline</atitle><jtitle>Behavioural brain research</jtitle><addtitle>Behav Brain Res</addtitle><date>2016-07-15</date><risdate>2016</risdate><volume>308</volume><spage>46</spage><epage>52</epage><pages>46-52</pages><issn>0166-4328</issn><eissn>1872-7549</eissn><abstract>•Male and female rats had no differences during maintenance and extinction.•Both males and females showed reinstatement to the CAF+CUES condition.•Male rats, but not females, reinstated to the NIC+CUES condition.•Varenicline alone attenuated NIC+CUES reinstatement in males.•Combination varenicline and progesterone decreased NIC+CUES reinstatement in males.
Tobacco use is the largest cause of preventable mortality in the western world. Even after treatment, relapse rates for tobacco are high, and more effective pharmacological treatments are needed. Progesterone (PRO), a female hormone used in contraceptives, reduces stimulant use but its effects on tobacco addiction are unknown. Varenicline (VAR) is a commonly used medication that reduces tobacco use. The present study examined sex differences in the individual vs. combined effects of PRO and VAR on reinstatement of nicotine-seeking behavior in a rat model of relapse. Adult female and male Wistar rats self-administered nicotine (NIC, 0.03mg/kg/infusion) for 14days followed by 21days of extinction when no cues or drug were present. Rats were then divided into 4 treatment groups: control (VEH+SAL), PRO alone (PRO+SAL), VAR alone (VEH+VAR) and the combination (PRO+VAR). Reinstatement of nicotine-seeking behavior induced by priming injections of NIC or caffeine (CAF), presentation of cues (CUES), and the combination of drugs and cues (e.g. NIC+CUES, CAF+CUES) were tested after extinction. Male and female rats did not differ in self-administration of nicotine or extinction responding, and both showed elevated levels of responding to the CAF+CUES condition. However, males, but not females, reinstated active lever-pressing to the NIC+CUES condition, and that was attenuated by both VAR and VAR+PRO treatment. Thus, males were more sensitive to NIC+CUE-induced reinstatement than females, and VAR alone and VAR combined with PRO effectively reduced nicotine relapse.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27091301</pmid><doi>10.1016/j.bbr.2016.04.023</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Behavioural brain research, 2016-07, Vol.308, p.46-52 |
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| subjects | Animals Disease Models, Animal Drug Combinations Drug-Seeking Behavior - drug effects Extinction, Psychological - drug effects Female Male Nicotine Nicotine - adverse effects Nicotinic Agonists - pharmacology Progesterone - pharmacology Progestins - pharmacology Rats Rats, Wistar Reinforcement Schedule Reinstatement Self Administration Sex differences Sex Factors Smoking Cessation Varenicline - pharmacology |
| title | Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline |
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