Neuroscience Letters 513 (2012) 214–218 Contents lists available at SciVerse ScienceDirect Neuroscience Letters j our nal ho me p ag e: www.elsevier.com/locate/neulet SKF 38393 reverses cocaine-conditioned place preference in mice Pamela Sabioni a , Vânia D’Almeida a , Monica L. Andersen a , Roberto Andreatini b , José C.F. Galduróz a,∗ a Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), Brazil b Department of Pharmacology, Universidade Federal do Paraná (UFPR), Brazil a r t i c l e i n f o Article history: Received 13 December 2011 Received in revised form 11 February 2012 Accepted 13 February 2012 Keywords: Cocaine Conditioned place preference Dopamine Mice SKF 38393 a b s t r a c t Cocaine is a psychotropic drug with a high potential for abuse due to its euphoric effects. Efforts to develop medications for the treatment of cocaine dependence have not been clinically successful. Some studies using animal models have shown positive effects of dopaminergic agents such as partial agonists of the dopamine D1 receptor. Thus, this study aimed to examine the effect of the dopamine D1 receptor partial agonist SKF 38393 on cocaine craving. Adult male C57BL/6J mice were injected with cocaine for 10 days in a conditioned place preference apparatus using a biased procedure and subsequently treated for three consecutive days with SKF 38393. The results showed that SKF 38393 was able to block the preference of cocaine-conditioned animals for the compartment paired with the drug without showing effects on locomotor activity. The results of this study suggest that partial activation of D1 dopamine receptors may be necessary for the development of pharmacotherapies for cocaine addiction. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Cocaine is a psychotropic drug its main mechanism of action is the blocking of dopamine transport in the mesolimbic sys- tem [11,22], consequently causing an increase in the available dopamine in the synaptic cleft. This increase is responsible for the euphoric effects of cocaine, thus making it a substance that has high potential for abuse. Dopamine acts on the different types of dopamine receptors, D1 and D2, which play opposite roles in drug- seeking behavior. The activation of D1 seems to decrease cocaine craving and inhibit its reinstatement, whereas D2 activation inten- sifies it [26]. The increase in the number of cocaine users has intensified efforts to develop medications for the treatment of cocaine depend- ence [31]. Based on pre-clinical studies, dopamine agonists and antagonists have been proposed as drug substitutes, maintenance drugs or cocaine antagonists [19]. However, these drugs have not been clinically successful [17,32] and may be associated with debil- itating side effects [16]. An alternative strategy in the dopamine approach to cocaine dependence treatment is the use of dopamin- ergic partial agonists [27]. This class of drugs does not maximally activate downstream signal transduction pathways and can exhibit a reduced potential for abuse compared with full agonists, in addi- tion to having less severe motor effects compared to the antagonists ∗ Corresponding author at: Department of Psychobiology, Universidade Federal de São Paulo, Rua Napoleão de Barros, 925, Vila Clementino, SP 04024-002 São Paulo, Brazil. Tel.: +55 11 2149 0168. E-mail address: galduroz@unifesp.br (J.C.F. Galduróz). [23]. For example, within the D1 family, the partial agonists SKF 38393 and SKF 75670 were shown to attenuate the discriminative stimulus and the behavioral stimulant effects of cocaine in monkeys and rodents [15,27]. They were also shown to antagonize cocaine by intravenous self-administration in rats and monkeys [2,4,14]. SKF 77434 reduced cocaine effects in monkeys [15,20] and mice [15]. Furthermore, SKF 38393 and another D1 partial agonist, SKF 83959, inhibited cocaine-seeking behavior, suggesting that these compounds may be effective in mitigating the effects of the drug [28]. Conditioned place preference is a method that has been widely used in animals to measure the reinforcing properties of drugs of abuse [33]; this method consists of measuring the effects of reinforcing events on behavior and is based on the hypothesis of associative memory. The administration of cocaine in rodents produces a positive and long-lasting conditioned place preference [3,5,7,12,25]. The objective of our study was to investigate, in an animal model, a possible method of pharmacological treatment for cocaine addiction that does not present debilitating consequences and that decreases drug craving. Thus, we examined the effect of SKF 38393, a D1 partial agonist, on cocaine-conditioned place pref- erence in mice. The expectation was to observe the reversing of the effects induced by cocaine after the administration of SKF 38393. Although most of the studies on conditioned place pref- erence test the experimental drug earlier in the conditioning trials, to block the acquisition phase, we made the choice to intro- duce the SKF 38393 after the installation of cocaine preference, to treat or reverse the cocaine effects. This late administration was an attempt to make a protocol that was closer to reality, in 0304-3940/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2012.02.041