Effects of Systemic Injections of Dopaminergic Agents on the Habituation of Rats Submitted to an Open Field Test

Many studies have reported that systemic injections of dopaminergic drugs result in profound changes in the behavior of animals in the open field. At the same time, it is hypothesized that increased brain dopaminergic activity prevents animals from habituating to a novel environment, and this effect would be responsible for the conditioned hyperactivity observed when rats are tested later in a drug-free state. However, little is known on the concurrent effects of these drugs, on learning processes and motor activity. To examine this issue, in the present study we assessed the effects of injections of the dopamine (DA) agonists amphetamine and apomorphine, the receptor antagonist chlorpromazine and the atypical neuroleptic clozapine on exploratory activity and habituation in rats exposed to the open field test. The observer scored the occurrence of animal behavior during three postinjection observation periods (0–5, 5–10 and 10–15 min). The results confirmed that amphetamine and apomorphine lead to a dose-dependent behavioral activation, while chlorpromazine produces an opposite effect, extending previous accounts of behavior of systemic-injected rats with these drugs. Independent of the level of motor activity, higher or lower than the control groups, habituation still occurs following DA agonists (amphetamine and apomorphine) and antagonist (chlorpromazine) injections in rats submitted to the open field test. Furthermore, the reduction of the exploratory activity over time in the open field after clozapine was less pronounced than in controls, in contrast to classical DA agents. The present results suggest that activation of DA mechanisms is involved in species-typical behaviors associated with exploratory behavior, but does not seem to be involved in non-associative learning processes, such as habituation. These effects could not be attributed to the decline in brain levels of the drugs during the session, as the behavioral activation remained high in rats previously habituated and injected with dopaminergic agonists within the same protocol. On the other hand, the atypical DA blocker clozapine reduced the expression of habituation, opening the possibility of involvement of alternative mechanisms, such as 5-HT mechanisms, in this non-associative learning process.