| First Author | Portugal GS | Year | 2008 |
| Journal | Neurobiol Learn Mem | Volume | 89 |
| Issue | 2 | Pages | 106-13 |
| PubMed ID | 17584502 | Mgi Jnum | J:129307 |
| Mgi Id | MGI:3769054 | Doi | 10.1016/j.nlm.2007.05.002 |
| Citation | Portugal GS, et al. (2008) beta2 subunit containing acetylcholine receptors mediate nicotine withdrawal deficits in the acquisition of contextual fear conditioning. Neurobiol Learn Mem 89(2):106-13 |
| abstractText | Acute nicotine enhances contextual fear conditioning, whereas withdrawal from chronic nicotine produces impairments. However, the nicotinic acetylcholine receptors (nAChR) that are involved in nicotine withdrawal deficits in contextual fear conditioning are unknown. The present study used genetic and pharmacological techniques to investigate the nAChR subtype(s) involved in the effects of nicotine withdrawal on contextual fear conditioning. beta2 or alpha7 nAChR subunit knockout (KO) and corresponding wild-type (WT) mice were withdrawn from 12 days of chronic nicotine treatment (6.3mg/kg/day), and trained with 2 conditioned stimulus (CS; 85dB white noise)-unconditioned stimulus (US; 0.57mA footshock) pairings on day 13. On day 14, mice were tested for contextual and cued freezing. beta2 KO mice did not show nicotine withdrawal-related deficits in contextual fear conditioning, in contrast to WT mice and alpha7 KO mice. A follow-up study investigated if nicotine withdrawal disrupts acquisition or recall of contextual fear conditioning. The high affinity nAChR antagonist dihydro-beta-erythroidine (DHbetaE; 3mg/kg) was administered prior to training or testing to precipitate withdrawal in chronic nicotine-treated C57BL/6 mice. Deficits in contextual fear conditioning were observed in chronic nicotine-treated mice when DHbetaE was administered prior to training, but not when administered at testing. These results indicate that beta2-containing nAChRs, such as the alpha4beta2 receptor, mediate nicotine withdrawal deficits in contextual fear conditioning. In addition, nicotine withdrawal selectively affects acquisition but not recall or expression of the learned response. |
