Dose-dependent aversive and rewarding effects of amphetamine as revealed by a new place conditioning apparatus

Cabib, Simona; Puglisi-Allegra, Stefano; Genua, C.; Simon, H.; Moal, Michel Le; Piazza, Pier Vincenzo

doi:10.1007/bf02247398

Cited by 41 publications

(25 citation statements)

References 19 publications

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Section: Discussionsupporting

confidence: 91%

“…For males, the highest dose used (3.0mg/kg) appears to be less effective than median doses (0.5 and 1.0mg/ kg). This is consistent with studies showing that higher doses of AMPH are less effective, or in fact, aversive [11].For females, the dose response was shifted leftward, with the lowest dose used (0.1mg/kg) showing a trend toward CPP and higher doses, that were effective in males (1.0 and 3.0mg/ kg), failing to induce CPP. This is consistent with previous studies in other species which showed that females were more sensitive to psychostimulants [7,49].…”

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confidence: 89%

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Amphetamine reward in the monogamous prairie vole

Aragona¹,

Detwiler²,

Wang³

2007

Neuroscience Letters

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Recent studies have shown that the neural regulation of pair bonding in the monogamous prairie vole (Microtus ochrogaster) is similar to that of drug seeking in more traditional laboratory rodents. Therefore, strong interactions between social behavior and drug reward can be expected. Here, we established the prairie vole as a model for drug studies by demonstrating robust amphetamineinduced conditioned place preferences in this species. For both males and females, the effects of amphetamine were dose-dependent, with females being more sensitive to drug treatment. This study represents the first evidence of drug reward in this species. Future studies will examine the effects of social behavior on drug reward and the underlying neurobiology of such interactions.Keywords drug abuse; addiction; conditioned place preference; attachment; social bonding; monogamy There are many factors that contribute to drug abuse. Included among these are genetic predisposition and drug availability, variables that have been well modeled with traditional laboratory rodents and that have been shown to greatly influence drug seeking behavior [1,18,22,59]. However, there are other complexities known to influence drug taking in humans, such as social environment [31]. This variable is more difficult to study in the laboratory because traditional rodent subjects do not exhibit social organization analogous to that shown by humans [4]. Studies in non-human primates demonstrate the importance of social hierarchy on drug taking [39]. However, primate experiments are not practical for most laboratories and therefore understanding the neurobiology of interactions between social behavior and drug abuse would be greatly facilitated if it were studied in rodent models. Here, we have taken an initial step toward this end by establishing a highly social rodent species, the monogamous prairie vole (Microtus ochrogaster), for drug studies.The prairie vole is a powerful model for studies of social attachment [13,23]. Males and females of this species show preferential mating with one partner [20], exhibit high levels of parental behavior [36][37][38]43], and form enduring pair bonds, which are maintained even if one member of the pair is lost [57]. Pair bond formation is routinely studied in the laboratory by using a partner preference test [60,61] and such studies have provided excellent insight into the neural regulation of pair bonding [62]. In particular, recent studies have shown that pair bond formation and maintenance critically depend on key components of brain reward circuitry, Correspondence to: Zuoxin Wang, Ph.D., Department of Psychology, Florida State University, Tallahassee, FL 32306-1270, Phone: 850-644-5057, Fax: 850-644-7739, E-mail: E-mail: zwang@psy.fsu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the res...

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Section: Discussionsupporting

confidence: 91%

supporting

confidence: 89%

Amphetamine reward in the monogamous prairie vole

Aragona¹,

Detwiler²,

Wang³

2007

Neuroscience Letters

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“…For the CPP experiments, the twocompartments differed only in the spatial organization of two vertical columns placed in each compartment (44). Thirty rats [OFF n = 7 (food) + 7 (cocaine); ON n = 13 (food) + 9 (cocaine)] were first exposed to both compartments for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Reducing the desire for cocaine with subthalamic nucleus deep brain stimulation

Rouaud

Lardeux

Panayotis

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

186

131

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Deep brain stimulation (DBS) is a reversible technique that is currently used for the treatment of Parkinson disease and may be suitable for the treatment of psychiatric disorders. Whether DBS inactivates the target structure is still a matter of debate. Here, from findings obtained in rats, we propose DBS of the subthalamic nucleus (STN) as a possible treatment for cocaine addiction to be further tested in human studies. We show that STN DBS reversibly reduces the motivation to work for an i.v. injection of cocaine, and it increases motivation to work for sucrose pellets. These opposite effects may result from STN DBS effect on the positive affective properties of these rewards. Indeed, we further show that STN DBS reduces the preference for a place previously associated with the rewarding properties of cocaine, and it increases the preference for a place associated with food. Because these findings are consistent with those observed after STN lesions [Baunez C, Dias C, Cador M, Amalric M (2005) Nat Neurosci 8:484-489], they suggest that STN DBS mimics an inactivation of the STN on motivational processes. Furthermore, given that one of the major challenges for cocaine addiction is to find a treatment that reduces the craving for the drug without diminishing the motivation for naturally rewarding activities, our findings validate STN as a good target and DBS as the appropriate technique for a promising therapeutic strategy in the treatment of cocaine addiction.O ver the past decade, there has been an increasing interest in neurosurgical procedures using deep brain stimulation (DBS) to treat neurological and psychiatric disorders, such as Parkinson disease (1, 2) and Huntington disease (3), as well as depression (4) and obsessive compulsive disorders (5).A recent study showing that the effects of subthalamic nucleus (STN) DBS mainly result from a stimulation of the cortico-STN fibers questioned the inactivation of STN by DBS (6). However, there was previously a consensus to consider that action of STN DBS as an inactivation of the cell bodies of the targeted structure with an activation of the passing fibers (7). The mechanisms of DBS remain thus a matter of debate.From the clinical point of view, DBS represents a reversible way to inactivate a particular structure in the brain, a strategy that is preferred to ablative surgery in most cases. The choice of the targeted structure is adapted to the disease.In the case of drug addiction, a devastating disorder whose hallmark feature is an uncontrolled motivation to take the drug while naturally rewarding activities are forsaken, it is crucial to decrease the compulsive motivation for the drug, at the same time preventing decreased motivation for alternative rewarding activities.Because cocaine acts by blocking the dopaminergic transporter, and therefore temporarily increases the amount of dopamine (DA) available in the brain, early treatments for addiction targeted DA system to counteract cocaine effects. However, it is now largely accepted that interfering with the ...

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“…The behavioral procedure was previously described (Cabib et al 1996). Briefly, on day 1 (pretest), mice were free to explore the entire apparatus for 20 min.…”

Section: Conditioned Place Preferencementioning

confidence: 99%