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However, it was recently reported that transgenic mice overexpressing a bacterial artificial chromosome containing <jats:italic>choline acetyltransferase<\/jats:italic> (<jats:italic>ChAT<\/jats:italic>) gene, for synthesizing the neurotransmitter acetylcholine, present with multiple <jats:italic>vesicular acetylcholine transporter<\/jats:italic> (<jats:italic>VAChT<\/jats:italic>) gene copies, resulting in altered cholinergic tone and accompanying behavioral abnormalities. Since ChAT::Cre+ rats, used increasingly for understanding the biological basis of CNS disorders, utilize the mouse ChAT promotor to control Cre recombinase expression, we assessed for similar genotypical and phenotypical differences in such rats compared to wild-type siblings. The rats were assessed for mouse <jats:italic>VAChT<\/jats:italic> copy number, VAChT protein expression levels and for sustained attention, response control and anxiety. Rats were also subjected to a contextual fear conditioning paradigm using an unconditional fear-inducing stimulus (electrical foot shocks), with blood samples taken at baseline, the fear acquisition phase and retention testing, for measuring blood plasma markers of hypothalamic\u2013pituitary\u2013adrenal gland (HPA)-axis activity. ChAT::Cre+ rats expressed multiple mouse <jats:italic>VAChT<\/jats:italic> gene copies, resulting in significantly higher VAChT protein expression, revealed anxiolytic behavior, hyperlocomotion and deficits in tasks requiring sustained attention. The HPA-axis was intact, with unaltered circulatory levels of acute stress-induced corticosterone, leptin and glucose. Our findings, therefore, reveal that in ChAT::Cre+ rats, <jats:italic>VAChT<\/jats:italic> overexpression associates with significant alterations of certain cognitive, motor and affective functions. Although highly useful as an experimental tool, it is essential to consider the potential effects of altered cholinergic transmission on baseline behavior in ChAT::Cre rats.<\/jats:p>","DOI":"10.1007\/s00429-019-01957-y","type":"journal-article","created":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T09:03:00Z","timestamp":1568106180000},"page":"3095-3116","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Altered motor, anxiety-related and attentional task performance at baseline associate with multiple gene copies of the vesicular acetylcholine transporter and related protein overexpression in ChAT::Cre+ rats"],"prefix":"10.1007","volume":"224","author":[{"given":"Craig P.","family":"Mantanona","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Alsi\u00f6","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna L.","family":"Elson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth M.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey W.","family":"Dalley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Bussey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilse S.","family":"Pienaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,10]]},"reference":[{"key":"1957_CR1","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/npp.2012.236","volume":"38","author":"L Agnoli","year":"2013","unstructured":"Agnoli L, Mainolfi P, Invernizzi RW, Carli M (2013) Dopamine D1-like and D2-like receptors in the dorsal striatum control different aspects of attentional performance in the five-choice serial reaction time task under a condition of increased activity of corticostriatal inputs. 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