Effects of selective dopamine D 1 - and D 2 -type receptor antagonists on the development of behavioral sensitization to 7-OH-DPAT

Abstract

The primary objective of this study was to determine whether the development of behavioral sensitization to the putative dopamine D3 receptor agonist 7-OH-DPAT could be prevented by either selective D1-type or D2-type dopamine receptor antagonists. In three experiments, male Wistar rats (250-350 g) were given seven to nine injections (at 48-h intervals) of 7-OH-DPAT (1.0 mg/kg, SC) or vehicle in combination with the D2-type dopamine antagonist eticlopride (0.3 mg/kg, SC), the D1-type dopamine antagonist SCH 23390 (0.1 or 0.2 mg/kg, SC), or vehicle. After the injections, the rats were tested for locomotor activity in photocell arenas for 2 h. In the first two experiments, after seven injections, all rats were tested for activity following vehicle injections to test for possible conditioning effects. In each experiment, after the last pre-exposure session, all rats were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) and tested for activity. Major findings were as follows: a) 7-OH-DPAT treatments produced a progressively greater increase in locomotor activity with repeated treatment; b) concurrent treatment with eticlopride or SCH 23390 (0.1 and 0.2 mg/kg) blocked the acute locomotor-activating effects of 7-OH-DPAT across days; c) eticlopride, but not SCH 23390, completely blocked the development of behavioral sensitization to 7-OH-DPAT. Although the low dose of SCH 23390 (0.1 mg/kg) produced a partial attenuation of sensitization, the higher dose (0.2 mg/kg) of SCH 23390 appeared to augment, rather than block, sensitization to 7-OH-DPAT; d) rats previously treated with SCH 23390 (0.2 mg/kg, but not 0.1 mg/kg) without 7-OH-DPAT displayed a hyperactive response to the 7-OH-DPAT challenge injection; and e) after vehicle injections, rats previously given 7-OH-DPAT, SCH 23390, or eticlopride either alone or in combination were more active than vehicle control rats. These findings suggest that the neurochemical mechanisms mediating the development of behavioral sensitization to 7-OH-DPAT may differ from those of other dopamine D2-type agonists such as quinpirole or bromocriptine. Moreover, these results demonstrate that hyperactivity responses following vehicle injections in drug-pretreated animals do not necessarily reflect conditioning mechanisms.

Deletion of SHATI/NAT8L increases dopamine D1 receptor on the cell surface in the nucleus accumbens, accelerating methamphetamine dependence

“…2c-f). D1-like dopamine receptor antagonist attenuates the expression of behavioural sensitization (Henry et al, 1998;Mattingly et al, 1998). Moreover, we found that METH-induced sensitization and CPP are enhanced in Nat8l KO mice (Fig.…”

Effects of SCH 23390 and eticlopride on cocaine-seeking produced by cocaine and WIN 35,428 in rats

“…This finding suggests that the effects of this low dose on WIN 35,428-produced drug-seeking do not reflect a non-specific effect of motor incapacitation. However, the decrease in cocaine-produced drug-seeking produced by the higher dose of eticlopride (0.3 mg/kg) may be the result of motoric disruption that is generally produced following higher dose administrations of eticlopride (Mattingly et al 1998). Indeed, in a previous paper (Green and Schenk 2002), the low dose of 0.1 mg/ kg eticlopride decreased caffeine-produced cocaine-seeking but increased responding maintained by cocaine selfadministration.…”

Apomorphine-induced context-specific behavioural sensitization is prevented by the D1 antagonist SCH-23390 but potentiated and uncoupled from contextual cues by the D2 antagonist sulpiride

“…amphetamine and cocaine). While indirect acting agonists activate all dopamine receptors, direct acting agonists are more selective and include D2 preferring agonists such as bromocriptine Wise 1992, 1993), mixed D1/D2 agonists such as apomorphine (Mattingly and Gotsick 1989;Braga et al 2009a, b) and mixed D2/D3 agonists such as quinpirole (Szechtman et al 1994;Rowlett et al 1995) and 7-OHDPAT (Mattingly et al 1998). It is also the case that these agonist-induced behavioural sensitization effects are typically contextspecific which indicates a contributory learning mechanism in this process.…”