Behavioral effects of amphetamine in streptozotocin-treated rats. Eur J Pharmacol

Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, United States.
European Journal of Pharmacology (Impact Factor: 2.53). 03/2008; 581(1-2):105-12. DOI: 10.1016/j.ejphar.2007.11.047
Source: PubMed


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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Available from: Aurelio Galli, Dec 31, 2013
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    • "However, studies of the consequences of reduced insulin signaling for behavioral responses to AMPH are mixed. Some report that decreased insulin status (e.g., STZ treatment) attenuates behavioral responses to AMPH (Galici et al., 2003; Marshall, 1978; Rowland et al., 1985), while others find no or only very modest effects of low insulin on the behavioral responses to AMPH and other DA targeting drugs (Owens et al., 2005a; Sevak et al., 2008a, b). These mixed results are not surprising given differences in experimental design, drug doses, number of drug exposures and the behavioral readout. "
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    • "For the next 8 daily 30-min sessions free-feeding (n=21) and food-restricted (n=19; 10g/day; testing began one week after the start of restriction) rats received either amphetamine (1.78 mg/kg, i.p.) or saline (1 ml/kg, i.p.) and were placed in a chamber equipped with a floor with only one texture (hole or grid, alternating across days and specifically paired with either drug or vehicle). A single dose of 1.78 mg/kg amphetamine was chosen for the following reasons: this dose reliably produced conditioned place preference in normal and in streptozotocintreated rats (Sevak et al., 2008); and four every-other-day injections of this dose normalized dopamine clearance and partially restored sensitivity to amphetamine-induced locomotion in streptozotocin-treated rats (Owens et al., 2005). Some rats (12 free-feeding and 12 foodrestricted ) received only saline in all eight conditioning trials to determine whether there was a preference for floor texture or side of the chamber. "
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