Effects of typical, atypical, and novel antipsychotic drugs on amphetamine‐induced place conditioning in rats

Abstract

Because amphetamine-induced place conditioning is believed to be mediated by dopamine (DA) receptors within the nucleus accurnbens, this behavioral model may be useful for detecting drugs with antipsychotic efficacy. To test the selectivity and specificity of the model, the present study examined whether amphetamine-induced place conditioning is reversible in rats pretreated with the classical antipsychotic haloperidol, the atypical antipsychotic clozapine, and the novel antipsychotics raclopride and risperidone. The non-antipsychotic drugs baclofen and prazosin were also tested. Male Sprdgue-Dawley rats received d-amphetamine (5.4 pmolikg ip) paired with one side of d two-compartment box and saline paired with the other side. During these pairings, locomotor activity was measured On the test day, the amount of time drug-free rats spent in each compartment was determined Rats trained with amphetamine alone showed a significant increase in time spent on the drug-paired side from pre-to postconditioning, indicating a place preference. Pretreatment with the highest dose of either haloperidol (0 026, 0.13, 0 26 p+mol/kg 5c), clozdpine (3, 15, 30, 60 pmolikg sc), raclopride (0 1 , 0.2, 1 0 pmol/kg), or risperidone (0 12, 0 24, 1 2 pmolikg sc) prior to amphetamine significantly blocked the establishment of place conditioning. Treatment with the antipsychotic alone did not support place conditioning (preference or aversion) On conditioning days, hdloperidol, clorapine, raclopride, and risperidone significantly decreased amphetamine-induced locomotor activity Pretreatment with either baclofen or prazosin failed to disrupt amphetarnine-induced place conditioning despite significant decreases in locomotor activity on the conditioning days These data provide preliminary cupport for amphetarnine place conditioning as a rodent model for detecting drugs with antipsychotic efficacy o 1995 Wllcy-Lls inc

α- and β-Adrenergic Receptors Differentially Modulate the Emission of Spontaneous and Amphetamine-Induced 50-kHz Ultrasonic Vocalizations in Adult Rats

“…Clonidine, for example, is self-administered IV (Davis and Smith, 1977) and induces CPP (Asin and Wirtshafter, 1985;Cervo et al, 1993) in rats, whereas prazosin seems motivationally neutral (Forget et al, 2009;Zarrindast et al, 2002). The inhibitory effect of prazosin is potentially interesting in view of its reported failure to block either the discriminative stimulus effects of AMPH in rats (Arnt, 1996;West et al, 1995) or the acquisition of AMPH CPP (Hoffman and Donovan, 1995).…”

Effects of dopamine receptor antagonists on the acquisition of ethanol-induced conditioned place preference in mice

“…Dopamine D2-like receptors also appear to be involved in drug reward, with studies showing that pretreatment with the antagonist haloperidol blocks the development of place conditioning with amphetamine (Banasikowski et al. 2012; Hoffman and Donovan 1995; Mithani et al 1986; Spyraki et al 1982), methylphenidate (Mithani et al 1986), heroin (Spyraki et al 1983) and morphine (Manzanedo et al 2001). More highly selective dopamine D2-like receptor antagonists like raclopride have also been shown to attenuate amphetamine- and morphine-induced conditioned place preference (CPP) acquisition (Hoffman and Donovan 1995; Manzanedo et al 2001).…”

Respective roles of dopamine D2 and D3 receptors in food-seeking behaviour in rats

“…However, antagonists at either DA receptor subclass counteract the appetitive effects of enhanced dopaminergic transmission (Carr et al 1989;Tzschentke 1998). In particular, D 2 -like receptor antagonists have been reported to reduce selectively amphetamine-and food-induced conditioned place preference (Spyraki et al 1982;Beninger and Hahn 1983;Hoffman and Donovan 1995), and cocaine reinforcing effects, as evaluated in self-administration procedures (Caine and Koob 1994).…”