European Neuropsychopharmacology, 2 (1992) 121--125 121 @ 1992 Elsevier Science Publishers B.V. All rights reserved 0924-977X/92/$05.00 ENP 00057 Additive effects of chronic treatment with antidepressant drugs and intermittent treatment with a dopamine agonist Mariusz Papp 1, Richard Muscat 2 and Paul Willner Department of Psychology, City of London Polytechnic, Old Castle St., London E1 7NT, UK (Received 11 November, 1991) (Revised, received 28 January, 1992) (Accepted 6 February, 1992) Key words': Antidepressant drugs; Imipramine; Amitriptyline; Mianserin; Quinpirole; Behavioral sensitization; Locomotor activity; (Rat) Summary Locomotor activity in response to the D2/D3 agonist quinpirole was studied in male rats treated chronically (25-40 days) with imipramine, amitriptyline or mianserin (5 mg/kg/day). All three antidepres- sants potentiated the response to quinpirole. Repeated administration of quinpirole at 3-day intervals also caused a marked increase in the locomotor response to quinpirole. Imipramine-treated animals were more active than vehicle-treated animals on all quinpirole trials. Animals tested in the locomotor activity apparatus for the first time following their fifth quinpirole injection showed sensitization, but to a lesser extent than animals tested repeatedly under quinpirole. This context-independent sensitization was potentiated by all three antidepressants. We discus the potential clinical relevance of these results. Introduction Antidepressant drugs have traditionally been assumed to exert their clinical effects through an interaction with noradrenergic or serotonergic systems. However, after chronic administration, antidepressants have also been found to potentiate the locomotor stimulant effects of dopamine (DA) D2/D3 agonists. These effects are apparent follow- ing systemic administration (Arnt et a1.,1984; Maj, 1988; Maj et al., 1984a,b; Martin-Iverson et al., 1Present address: Institute of Pharmacology, Polish Acad- emy of Sciences, Krakow, Poland. 2present address. Dept. of Biomedical Sciences, University of Malta, Msida, Malta. Correspondence to: Paul Willner, Department of Psychol- ogy, City of London Polytechnic, Old Castle St., London El 7NT, UK. Tel.: (+44 71) 320-1074; Fax: (+44 71) 320-1117. 1983; Willner and Montgomery, 1981) or direct injection of D2/D3 agonists into the nucleus accumbens (Maj, 1988; Maj and Wedzony, 1985, 1988; Maj et al., 1987). Studies in animal models of depression suggest that this increase in DA receptor responsiveness may be responsible for some of the therapeutic actions of antidepressants. For example, we have previously demonstrated that acute administration of DA receptor antago- nists reversed the therapeutic effect of antidepres- sants in animals displaying stress-induced anhedonia, at doses that were inactive in non- stressed animals or in untreated stressed animals (Muscat et al., 1990; Sampson et al., 1991). Others have reported a similar reversal of antidepressant actions by acute administration of DA receptor antagonists in the Porsolt forced swim test (Borsini et al., 1985; Pulvirenti and Samanin, 1986; Cervo and Samanin, 1987).