Effects of Continuous Exposure to Light on Behavioral Dopaminergic Supersensitivity Vanessa C. Abı ´lio, Fa ´bio M. Freitas, Miriam S. Dolnikoff, Ana Maria L. Castrucci, and Roberto Frussa-Filho Background: This study examines the effects of long-term continuous exposure to light on dopaminergic supersensi- tivity induced by repeated treatment with haloperidol in rats. Methods: Spontaneous general activity in an open-field (SGA) and stereotyped behavior induced by apomorphine (SB-APO) or amphetamine (SB-AMP) were used as exper- imental parameters. Rats were allocated to four groups in each experiment: saline-treated animals kept under a 12-hour light/dark cycle (LD) or 24-hour light/light cycle (LL), and 2 mg/kg haloperidol-treated animals kept under the above cycles. Plasma corticosterone concentration was also measured by radioimunoassay in saline-treated rats kept under a LD or LL cycle. Results: All the behavioral parameters used showed the development of central dopaminergic supersensitivity in rats kept under both cycles. Continuous exposure to light enhanced SGA and SB-AMP in both saline- and haloper- idol-treated rats, but did not modify SB-APO. Animals kept under the LL cycle presented an increased plasma corticosterone concentration. Conclusions: Our results suggest that continuous expo- sure to light leads to an increase in dopaminergic function in both normal and “supersensitive” rats. This effect seems to be mediated by a presynaptic mechanism possi- bly involving corticosterone actions. Biol Psychiatry 1999;45:1622–1629 © 1999 Society of Biological Psychi- atry Key Words: Light, melatonin, dopamine, stress, rat, behavior Introduction T he central nervous system is not static and immutable. Neuronal circuitry is highly adaptable and can main- tain homeostasis in response to internal and/or external perturbation. In rats, abrupt withdrawal from long-term haloperidol (Bernardi and Palermo-Neto 1979; Vital et al 1995; Queiroz and Frussa-Filho 1997), bromopride (Felı ´- cio et al 1987), metoclopramide (Frussa-Filho and Pal- ermo-Neto 1988), or sulpiride (Frussa-Filho and Palermo- Neto 1990) treatment enhanced not only the general activity observed in an open-field but also the responses to apomorphine-induced stereotyped behavior. These effects have been considered to be a consequence of the devel- opment of supersensitivity of central dopaminergic path- ways (Palermo-Neto 1982). Indeed, behavioral supersen- sitivity is thought to result from receptor site proliferation in mesolimbic and striatal brain tissues in response to chronic dopamine receptor blockade (Burt et al 1977; Muller and Seeman 1978; Fleminger et al 1983; Vital et al 1998). From a clinical point of view, whereas striatal dopaminergic supersensitivity has been proposed as a possible contributing factor to the development of tardive dyskinesia in schizophrenics receiving long-term neuro- leptic treatment (Klawans 1973; Latimer 1995; Ebadi and Srinivasan 1995; Casey 1995), mesolimbic dopaminergic supersensitivity has been suggested to be related to neu- roleptic-induced psychosis (Chouinard et al 1978; Choui- nard and Jones 1980) as well as to the increased respon- siveness to drugs such as cocaine in human stimulant abusers chronically treated with neuroleptics (LeDuc and Mitteman 1993). It is therefore important to identify drug and environmental variables which promote or attenuate dopaminergic supersensitivity. In this respect, while the effects of drug-related factors such as dose, duration, and schedule of treatment, on dopaminergic supersensitivity have received some attention (Bernardi and Palermo-Neto 1979; Bernardi et al 1981; Dewey and Fibiger 1983; Frussa-Filho and Palermo-Neto 1988; Frussa-Filho 1991; Frussa-Filho et al 1997), the effects of environmental variables have been much less studied. Within this context, the importance of lighting condi- tions in mediating the effects of repeated dopaminergic agonists administration on motor function and plasticity has been well established. Indeed, both sensitization and tolerance to the locomotor stimulant effect of continuously infused dopamine D 2 receptor agonist occur, depending on From the Departamento de Farmacologia, Escola Paulista de Medicina/UNIFESP (VCA, FMF, RFF); Departamento de Fisiologia, Escola Paulista de Medicina/ UNIFESP (MSD); and Departamento de Fisiologia, Instituto de Biocie ˆn- cias/USP (AMLC), Sa ˘o Paulo, Brazil. Address reprint requests to Dr. Roberto Frussa Filho, Escola Paulista de Medicina/ UNIFESP, Edificio Jose ´ Leal Prado, Rua Botucatu, 862 CEP 04023-062, Sa ˜o Paulo, SP, Brazil. Received April 21, 1997; revised January 30, 1998; accepted July 30, 1998. © 1999 Society of Biological Psychiatry 0006-3223/99/$20.00 PII S0006-3223(98)00305-9