Effects of dopamine agonists and antagonists on PCP-induced stereotyped behaviour and social isolation in the rat social interaction test.

Phencyclidine (PCP) induces behaviors in rats that model aspects of schizophrenia, including hyperactivity, stereotyped behavior, and social isolation. Over a 3-day regimen, dopamine D1-receptor agonists had limited effects on these PCP-induced behaviors, while the D1-antagonist SCH 23391 reduced PCP-induced social isolation, though tolerance developed after 21 days of treatment. The D2/D3/D4-agonist quinpirole worsened and mimicked PCP's social deficits, and the D2/D3-antagonist (-)sulpiride reduced PCP-induced stereotyped behavior and social isolation. A D4-antagonist had no effect. However, similar effects occurred in vehicle-treated rats, suggesting non-specific influences may have been involved.

Study at a glance

Abstract

Phencyclidine (PCP) can induce a model psychosis in humans that resembles an acute schizophrenic psychosis. In animal models of schizophrenia, PCP induces locomotor hyperactivity, stereotyped behaviour and social isolation, and the purpose of the present study was to describe the ability of dopamine agonists and antagonists to mimic or interact with these PCP-induced behaviours in rats. The compounds were administered daily for 3 days in combination with vehicle or 2.0 mg/kg PCP and the rats were tested in the social interaction test on the last day of drug administration. The study showed that D1-agonists with relative differences in efficacy at the DA-stimulated adenylate cyclase had limited effects on the PCP-induced behaviours, whereas the D1-antagonist SCH 23391 could alleviate the PCP-induce social isolation following daily treatment for 3 days. However, following long-term treatment for 21 days, the rats develop tolerance to this effect. These data thus suggested that the D1-receptor system only had a modulatory effect on PCP. In contrast, the D2-receptor family may be more directly involved, because the D2/D3/D4-agonist quinpirole could mimic and potentiate the PCP-induced deficits in social behaviour, and the D2/D3-antagonist (-)sulpiride could alleviate the PCP-induced stereotyped behaviour and social isolation. However, a D4-antagonist did not affect the behaviour of vehicle- and PCP-treated rats, suggesting that this system plays a less direct role in the behavioural effects of PCP. In general, however, the effects of SCH 23391, quinpirole and (-)sulpiride on the PCP-induced behaviours were mirrored in the vehicle-treated control groups and it is therefore possible that non-specific effects may have been important.