HIGH-DOSE SUBCHRONIC IMIPRAMINE TREATMENT - EFFECTS ON ANXIETY-LIKE (CONFLICT) BEHAVIOR IN RATS

In the management of both anxiety and depression, agents such as imipr amine (IMI) are noted for their 3-5 week delay to onset of clinical ef fect. A similar delay to onset has been reported for the anxiolytic-li ke (i.e., anticonflict) effect of chronic IMI treatment (2.5 mg/kg, BI D for 5 weeks) in the Conditioned Suppression of Drinking (CSD) confli ct paradigm; similar effects have been reported with other antidepress ants and in other conflict procedures. In contrast, in the Forced Swim Test (FST) model of depression, antidepressant-like effects are repor ted immediately following subchronic treatment with relatively high do ses of these agents (e.g., 30 mg/kg IMI, 3 times in 24 hr). The presen t study examined the effects of this high-dose, subchronic treatment w ith IMI on CSD conflict behavior. Conflict-trained female Sprague Dawl ey rats were divided into three groups with comparable pretreatment ba selines for shocks received. Treatments (0, 15, and 30 mg/kg IMI) were administered intraperitoneally (IF) at 23, 5, and 1 hr prior to CSD c onflict testing on day 1; CSD conflict behavior was then monitored dai ly (Mon-Fri) for 5 weeks following treatment. IMI treatment (30 and, t o a lesser extent, IS mg/kg) significantly reduced shocks received (pu nished responding) and water intake (unpunished responding) on day 1; although water intake was also slightly reduced in both IMI treatment groups for the remainder of test week 1, there was no difference In sh ocks received between the various treatments for this period Subjects receiving 30 mg/kg IMI (bat not those receiving 15 mg/kg IMI or vehicl e) accepted significantly more shocks than controls on weeks 2-4 (maxi mal increase at week 3) and returned to pretreatment baseline levels b y week 5. This, subchronic high-dose treatment with IMI (and perhaps o ther antidepressants) produces anxiolytic-like effects which are delay ed in nature and persist for several weeks after treatment. (C) 1995 W iley-Liss, Inc.