Amphetamines are known to enhance alertness, mood, motivation and motor performance. Chronic use of amphetamines is associated with addiction and mental conditions including mood, psychotic, obsessive and compulsive disorders. These known effects of amphetamines may suggest that amphetamine administration alters motivational and cognitive processes that integrate sensory information for action. To study effects of damphetamine on such integrative processes, we employed sensation seeking of unconditioned visual stimuli (VS). Specifically, our procedure required rats to lever-press to obtain a flash of light, which is weakly reinforcing in rats. Because amphetamines effects on drug seeking and mental conditions can be exacerbated by stress, we also examined effects of stress induced by chronic food-restriction and its interaction with amphetamine on VS seeking. We found that in chronically food-restricted (FR) rats (85-90% of their original weights), intraperitoneal (IP) injections of 1 mg/kg amphetamine markedly increased lever-pressing reinforced by VS, while the 0.3-mg/kg dose had no reliable effect, and the 3-mg/kg dose reliably decreased VS seeking. Locomotor activity of FR rats during these tests was affected somewhat differently than VS seeking: The 1-mg/kg dose increased locomotor activity, and the 3-mg/kg dose increased it even more. Unlike FR rats, rats that were given ad libitum (AD) access to food did not reliably increase VS seeking when treated with these doses of amphetamine, while significantly increasing locomotor activity. We also examine effects of the length of food restriction on amphetamine-induced VS seeking. Food deprivation of 24 hours or FR of 3 or 7 days with amphetamine injections (1mg/kg) did not increase VS seeking , while a 2 week FR significantly increased VS seeking, suggesting that chronic food restriction is needed for amphetamine to increase VS seeking. We also examined effects of repeated injections (8 times over 2 weeks) of amphetamine (1 mg/kg, IP) followed by a 3-week incubation. When challenged with 0.1-1 mg/kg amphetamine after incubation, prior amphetamine exposure did not have clear effects on VS seeking in FR or AD rats, but had sensitizing effects on locomotor activity. However, the whole procedure consisting of repeated injections (either saline or amphetamine) followed by a 3-week incubation made FR rats more sensitive to the effects of amphetamine on VS seeking. While FR rats were not different from AD rats in VS seeking without amphetamine, FR rats with prior saline- or amphetamineexposure significantly increased VS seeking with treatments of 0.3 or 1 mg/kg amphetamine. In summary, these results suggest that food restriction is an importnat factor in amphetamine-induced VS seeking, but not in locomotor activity. Neural mechanisms that amphetamine modulates to facilitate VS seeking may be substantially different from those of locomotor activity.

Project Start
Project End
Budget Start
Budget End
Support Year
14
Fiscal Year
2013
Total Cost
$477,861
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
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State
Country
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Keller, Kristine L; Vollrath-Smith, Fiori R; Jafari, Mehrnoosh et al. (2014) Synergistic interaction between caloric restriction and amphetamine in food-unrelated approach behavior of rats. Psychopharmacology (Berl) 231:825-40
Ikemoto, Satoshi; Bonci, Antonello (2014) Neurocircuitry of drug reward. Neuropharmacology 76 Pt B:329-41
Shin, Rick; Ikemoto, Satoshi (2010) Administration of the GABAA receptor antagonist picrotoxin into rat supramammillary nucleus induces c-Fos in reward-related brain structures. Supramammillary picrotoxin and c-Fos expression. BMC Neurosci 11:101
Liu, Zhong-Hua; Shin, Rick; Ikemoto, Satoshi (2008) Dual role of medial A10 dopamine neurons in affective encoding. Neuropsychopharmacology 33:3010-20
Shin, Rick; Qin, Mei; Liu, Zhong-Hua et al. (2008) Intracranial self-administration of MDMA into the ventral striatum of the rat: differential roles of the nucleus accumbens shell, core, and olfactory tubercle. Psychopharmacology (Berl) 198:261-70