Associative and nonassociative learning after chronic imipramine in rats

We investigated effects of 15 daily injections of imipramine (20 mg/kg; in one experiment also 10 and 30 mg/kg). The associative teaming types (place teaming and object recognition) as well as nonassociative teaming (habituation of exploration in an open field and within the object recognition test) were studied. Tests were performed immediately after the final injection (early test) and 24 h after the final injection (late test). The 5-HT1A, 5-HT1B/D, 5-HT2A, beta-adrenergic, D-2 receptors were assayed 24 h after the final injection and the 5-HT2A and beta-adrenergic receptors were also measured 60 and 96 h after the final injection. While associative types of teaming were impaired in early tests, they remained unaffected in late tests and, while the nonassociative teaming (habituation of exploration) remained unaffected in early tests, it was changed in late tests. Measured 24 h after the final injection, imipramine (20 and 30 mg/kg per day) down-regulated the concentration of beta-adrenergic and 5-HT2A receptors, while leaving all other measured receptors unaffected. However, only the down-regulation of the 5-HT2A receptor outlasted the initial 24-h period after the final injection. On the basis of present and previous results, we interpret the impairment of associative types of teaming in early tests as a reflection of anticholinergic effects of imipramine, while the modifications of habituation of exploration in late tests are likely primarily to be mediated by imipramine-provoked regulations of serotonergic receptors. (C) 2003 Elsevier Inc. All rights reserved.