Measuring reward with the conditioned place preference paradigm: a comprehensive review of drug effects, recent progress and new issues

In addition to its role in motor and attentional processes, the subthalamic nucleus (STN) has also been recently demonstrated to be involved in motivational function. Indeed, bilateral STN lesions modulate differentially the motivation for natural rewards and drugs of abuse, increasing motivation for food and decreasing motivation for cocaine in rats. Here, we show that in outbred rats, the STN can modulate the motivation for alcohol according to alcohol preference, without affecting alcohol intake. When performed on 'HighDrinker' rats, STN lesions enhanced the breaking point (BP) under a progressive ratio schedule of reinforcement and increased the time spent in the environment previously paired with alcohol access in the place preference paradigm. In contrast, when performed on 'Low-Drinker' rats, STN lesions decreased the BP and increased the time spent in the environment paired with water. These results show that STN lesions enhance the motivation for alcohol in rats showing a high alcohol preference, whereas they decrease it in rats showing a low preference for alcohol. These results suggest that the STN plays a complex role in the reward circuit, that is not limited to a dissociation between motivation for natural rewards and drugs of abuse, but takes other factors, such as alcohol preference, into account.

Section: Discussionmentioning

confidence: 42%

Alcohol Preference Influences the Subthalamic Nucleus Control on Motivation for Alcohol in Rats

Lardeux

Baunez

2007

“…The dose of memantine used in the present experiment (7.5 mg/kg), that inhibited conditioned morphine reward was also shown not to produce conditioned place preference or aversion (Popik and Danysz, 1997). Moreover, since it is known that the effects of NMDA receptor antagonists on morphine-induced CPP are not because of the state-dependent learning (Tzschentke, 1998), it may be speculated that the effects of 2-PMPA were also probably not because of the statedependent learning phenomenon.…”

Section: Effects Of Gcp II Inhibition On Morphine-induced Conditionedmentioning

confidence: 50%

Morphine Tolerance and Reward but not Expression of Morphine Dependence are Inhibited by the Selective Glutamate Carboxypeptidase II (GCP II, NAALADase) Inhibitor, 2-PMPA

Popik

Kozela

Wróbel

et al. 2002

Inhibition of glutamate carboxypeptidase II (GCP II; NAALADase) produces a variety of effects on glutamatergic neurotransmission. The aim of this study was to investigate effects of GCP II inhibition with the selective inhibitor, 2-PMPA, on: (a) development of tolerance to the antinociceptive effects, (b) withdrawal, and (c) conditioned reward produced by morphine in C57/Bl mice. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily (b.i.d.) administration of 2-PMPA and 10 mg/kg of morphine. Opioid withdrawal was measured 3 days after twice daily morphine (30 or 10 mg/kg) administration, followed by naloxone challenge. Conditioned morphine reward was investigated using conditioned place preference with a single morphine dose (10 mg/kg). High doses of 2-PMPA inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist, memantine) while not affecting the severity of withdrawal. A high dose of 2-PMPA (100 mg/kg) also significantly potentiated morphine withdrawal, but inhibited both acquisition and expression of morphine-induced conditioned place preference. Memantine inhibited the intensity of morphine withdrawal as well as acquisition and expression of morphine-induced conditioned place preference. In addition, 2-PMPA did not affect learning or memory retrieval in a simple two-trial test, nor did it produce withdrawal symptoms in morphinedependent, placebo-challenged mice. Results suggest involvement of GCP II (NAALADase) in phenomena related to opioid addiction.

“…The D1 receptor plays a critical role in mediating the behavioral and cellular effects of cocaine. For example, D1 receptor agonists and antagonists can affect cocaine-induced locomotor responses, discriminative stimulus, reinforcing effects, and reinstatement in a variety of experimental animal systems (Cabib et al, 1991;Caine and Koob, 1994;Tella, 1994;Cervo and Samanin, 1995;Pruitt et al, 1995;Self et al, 1996;Grech et al, 1996;Baker et al, 1998;Tzschentke, 1998;Caine et al, 1999Caine et al, , 2000Katz et al, 1999;Khroyan et al, 2000;Anderson et al, 2003;Nazarian et al, 2004). Repeated cocaine injections also lead to persistent increases in D1 receptor sensitivity within the NAc (Henry and White, 1995).…”

Section: Introductionmentioning

confidence: 99%

Repeated Cocaine Administration Induces Gene Expression Changes through the Dopamine D1 Receptors

Zhang

Tang

et al. 2005

Drug addiction involves compulsive drug-seeking and drug-taking despite known adverse consequences. The enduring nature of drug addiction suggests that repeated exposure to abused drugs leads to stable alterations that likely involve changes in gene expression in the brain. The dopamine D1 receptor has been shown to mediate the long-term behavioral effects of cocaine. To examine how the persistent behavioral effects of cocaine correlate with underlying changes in gene expression, we have used D1 receptor mutant and wild-type mice to identify chronic cocaine-induced gene expression changes mediated via the D1 receptors. We focused on the caudoputamen and nucleus accumbens, two key brain regions that mediate the long-term effects of cocaine. Our analyses demonstrate that repeated cocaine administration induces changes in the expression of 109 genes, including those encoding the stromal cell-derived factor 1, insulin-like growth factor binding protein 6, sigma 1 receptor, regulators of G-protein signaling protein 4, Wnt1 responsive Cdc42 homolog, Ca 2 þ /calmodulin-dependent protein kinase II a subunit, and cyclin D2, via the D1 receptors. Moreover, the seven genes contain AP-1 binding sites in their promoter regions. These results suggest that genes encoding certain extracellular factors, membrane receptors and modulators, and intracellular signaling molecules, among others, are regulated by cocaine via the D1 receptor, and these AP-1 transcription complex-regulated genes might contribute to persistent cocaine-induced behavioral changes.