Insulin Replacement Restores the Behavioral Effects of Quinpirole and Raclopride in Streptozotocin-Treated Rats

Sevak, Rajkumar J.; Koek, Wouter; Galli, Aurelio

doi:10.1124/jpet.106.115600

Cited by 27 publications

(38 citation statements)

References 34 publications

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“…A separate group of eight free-feeding rats were studied with cumulative doses of quinpirole alone and in combination with several different DA receptor antagonists: the D3 receptor-selective antagonist PG01037 (32.0 and 56.0 mg/kg s.c.), the D2 receptor-selective antagonist L-741,626 (1.0 and 3.2 mg/kg s.c.), and the nonselective D3/D2 receptor antagonist raclopride (0.032 and 0.056 mg/kg s.c.). The doses of L-741,626, PG01037, and raclopride studied were shown by others to have antagonist actions at dopamine receptors (Collins et al, 2005;Sevak et al, 2007). Antagonists were administered 30 min before administration of the first dose of quinpirole.…”

Section: Methodsmentioning

confidence: 99%

Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats

Baladi

Newman

2009

J Pharmacol Exp Ther

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The discriminative stimulus effects of dopamine (DA) D3/D2 receptor agonists are thought to be mediated by D2 receptors. To maintain responding, access to food is often restricted, which can alter neurochemical and behavioral effects of drugs acting on DA systems. This study established stimulus control with quinpirole in free-feeding rats and tested the ability of agonists to mimic and antagonists to attenuate the effects of quinpirole. The same antagonists were studied for their ability to attenuate quinpirole-induced yawning and hypothermia. DA receptor agonists apomorphine and lisuride, but not amphetamine and morphine, occasioned responding on the quinpirole lever. The discriminative stimulus effects of quinpirole were attenuated by the D3 receptor-selective antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide HCl (PG01037) and the nonselective D3/D2 receptor antagonist raclopride, but not by the D2 receptor-selective antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl-1H-indole (L-741,626); the potencies of PG01037 and raclopride to antagonize this effect of quinpirole paralleled their potencies to antagonize the ascending limb of the quinpirole yawning dose-response curve (thought to be mediated by D3 receptors). L-741,626 selectively antagonized the descending limb of the quinpirole yawning dose-response curve, and both L-741,626 and raclopride, but not PG01037, antagonized the hypothermic effects of quinpirole (thought to be mediated by D2 receptors). Food restriction (10 g/day/7 days) significantly decreased quinpirole-induced yawning without affecting the quinpirole discrimination. Many discrimination studies on DA receptor agonists use food-restricted rats; together with those studies, the current experiment using free-feeding rats suggests that feeding conditions affecting the behavioral effects of direct-acting DA receptor agonists might also have an impact on the effects of indirect-acting agonists such as cocaine and amphetamine.Many drugs of abuse as well as many drugs used in the clinic have actions on dopamine (DA) systems; however, there are a number of different DA receptors [i.e., D1-like (D1 and D5) and D2-like (D2, D3, and D4)], and the relative contribution of each receptor subtype to the abuse or therapeutic effects of drugs is not known. For example, DA D3 and D2 receptors are thought to mediate many of the behavioral effects of cocaine because some D3/D2 receptor agonists share behavioral (e.g., discriminative stimulus) effects with cocaine (Caine and

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Section: Methodsmentioning

confidence: 99%

Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats

Baladi

Newman

2009

J Pharmacol Exp Ther

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“…Streptozotocin-treated rats used for the schedule-controlled responding study were food-restricted, which might have contributed to the lack of significant change observed with these drugs. Indeed, sensitivity to behavioral effects of other drugs is dramatically changed by streptozotocin and by food restriction (Carr et al, 2002;Sevak et al, 2005Sevak et al, , 2007a.…”

Section: Discussionmentioning

confidence: 99%

“…That dopamine transporter activity is restored after several injections of amphetamine (Owens et al, 2005) suggests that a mechanism other than or in addition to altered dopamine transporter activity contributes to the acute behavioral effects of amphetamine. For example, other components of dopamine neurotransmission (receptor number or sensitivity) are changed after streptozotocin treatment (Sevak et al, 2007a), perhaps compensating for changes in dopamine transporter activity. Norepinephrine and serotonin also might play a role in the behavioral effects of stimulants since amphetamine has affinity for several types of monoamine transporters (Han and Gu, 2006;Rothman and Baumann, 2003;Uhl et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…For example, alloxan-induced diabetes attenuated amphetamine-induced stereotypy and locomotor-stimulation; insulin restored sensitivity to these drug effects (Marshall, 1978). The behavioral effects of drugs acting directly at dopamine receptors also are changed by streptozotocin (Rowland et al, 1985) or by restricted access to food (Sevak et al, 2007a), and food restriction is known to enhance self-administration as well as the motor-activating effects of several drugs of abuse, including cocaine and amphetamine (Campbell and Fibiger, 1971;Carroll et al, 1981;Carroll and Stotz, 1983). Amphetamine and cocaine decrease the threshold for lateral hypothalamic self-stimulation and this effect is further augmented by food restriction (Carr, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…These effects appear to be the result of insulin acting on receptors (insulin, IGF-1) since inhibition of insulin signaling caused dopamine transporters to be translocated away from the plasma membrane, thereby reducing dopamine transport (Carvelli et al, 2002;Garcia et al, 2005). In addition to effects on dopamine uptake, insulin can also modulate other components of the dopamine system; for example, hypoinsulinemic rats show decreased synthesis (Saller, 1984) and turnover (Kwok and Juorio, 1986;Lim et al, 1994) of dopamine and they are hyporesponsive to the behavioral effects of direct-acting dopamine drugs (Sevak et al, 2007a).…”

Section: Introductionmentioning

confidence: 99%

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Behavioral effects of amphetamine in streptozotocin-treated rats

Sevak

Koek

Daws

et al. 2008

European Journal of Pharmacology

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Experimentally-induced diabetes can modify the behavioral and neurochemical effects of drugs acting on dopamine systems, possibly through insulin-related regulation of dopamine transporter activity. In this study, several behavioral procedures were used to examine possible changes in sensitivity to amphetamine and other drugs in rats rendered diabetic by a single injection of streptozotocin. Conditioned place preference developed to food (Froot Loops ® ) in both control and diabetic rats, demonstrating that conditioned place preference with tactile stimuli can occur in streptozotocin-treated rats. Baseline locomotion was lower in streptozotocin-treated as compared to control rats, although amphetamine significantly increased locomotion in all rats. Conditioned place preference developed to amphetamine regardless of whether rats had received streptozotocin or saline. A second study compared the potency of drugs to decrease lever pressing maintained by food, before and after streptozotocin treatment. Gamma-hydroxybutyrate and amphetamine were less potent after streptozotocin while the potency of raclopride, quinpirole, ketamine, haloperidol and cocaine was not significantly changed by streptozotocin. While markedly affecting locomotion, body weight and blood glucose, streptozotocin only modestly affected sensitivity to the behavioral effects of amphetamine and other drugs; these results fail to confirm previous reports of decreased behavioral actions of stimulants in diabetic rats.

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Influence of body weight and type of chow on the sensitivity of rats to the behavioral effects of the direct-acting dopamine-receptor agonist quinpirole

Baladi

Newman

2011

Psychopharmacology

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Rationale Amount and type of food can alter dopamine systems and sensitivity to drugs acting on those systems. Objectives This study examined whether changes in body weight, food type, or both body weight and food type contribute to these effects. Methods Rats had free or restricted access (increasing, decreasing, or maintaining body weight) to standard (5.7% fat) or high fat (34.3%) chow. Results In rats gaining weight with restricted or free access to high fat chow, both limbs of the quinpirole yawning dose-response curve (0.0032–0.32 mg/kg) shifted leftward compared with rats eating standard chow. Restricting access to standard or high fat chow (maintaining or decreasing body weight) decreased or eliminated quinpirole-induced yawning; within one week of resuming free feeding, sensitivity to quinpirole was restored, although the descending limb of the dose-response curve was shifted leftward in rats eating high fat chow. These are not likely pharmacokinetic differences because quinpirole-induced hypothermia was not different among groups. PG01037 and L-741,626 antagonized the ascending and descending limbs of the quinpirole dose-response curve in rats eating high fat chow, indicating D3 and D2 receptor mediation, respectively. Rats eating high fat chow also developed insulin resistance. Conclusions These results show that amount and type of chow alter sensitivity to a direct-acting dopamine receptor agonist with the impact of each factor depending on whether body weight increases, decreases, or is maintained. These data demonstrate that feeding conditions, perhaps related to insulin and insulin sensitivity, profoundly impact the actions of drugs acting on dopamine systems.

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Insulin Replacement Restores the Behavioral Effects of Quinpirole and Raclopride in Streptozotocin-Treated Rats

Cited by 27 publications

References 34 publications

Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats

Dopamine D3 Receptors Mediate the Discriminative Stimulus Effects of Quinpirole in Free-Feeding Rats

Behavioral effects of amphetamine in streptozotocin-treated rats

Influence of body weight and type of chow on the sensitivity of rats to the behavioral effects of the direct-acting dopamine-receptor agonist quinpirole

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