Cognitive Sequelae of Intravenous Amphetamine Self-Administration in Rats: Evidence for Selective Effects on Attentional Performance

Abstract

Characterizing the nature and severity of cognitive deficits associated with chronic stimulant abuse may provide new insights into the neural substrates of drug addiction because such deficits may contribute to the chronic relapsing nature of compulsive drug use. This investigation examines in rats the long-term cognitive consequences of intravenously self-administered amphetamine, specifically on performance of a 5-choice serial reaction time task (5-CSRTT), which assesses visuo-spatial attention and impulsivity. Rats experienced 5 days of intravenous (i.v.) amphetamine self-administration and were then withdrawn for a period of 9 days, during which time testing on the 5-CSRTT took place. This was repeated on five consecutive occasions for a period of 10 weeks. Controls experienced identical training on the 5-CSRTT but during the self-administration sessions received yoked i.v. infusions of normal saline. The results reveal a selective and reproducible pattern of deficits on the 5-CSRTT following repeated withdrawal from amphetamine self-administration, with deleterious effects on the speed and accuracy of responding as well as increased omission errors. Premature (impulsive) responding, perseveration, and food consumption latencies were not significantly affected. Deficits in attentional performance fully recovered 4-5 days after amphetamine cessation and there was no evidence of any long-term disturbances, even when the attentional load was increased. However, following a 2-month abstinence period, abnormalities in the subsequent effects of acute noncontingent amphetamine were found, with increased omissions, slower response times, and reduced impulsivity. Thus, contingent i.v. amphetamine administration has both short-and long-term consequences, which may be relevant to the complex disturbances that accompany drug addiction.

Persistent Alterations in Cognitive Function and Prefrontal Dopamine D2 Receptors Following Extended, but Not Limited, Access to Self-Administered Cocaine

“…However, a more likely reason is that in the five-choice serial reaction time task all trials are signal trials, in that animals are required to report the location of a brief visual stimulus. We also saw only a transient deficit on signal trials, and in this sense the results reported here are consistent with those reported by Dalley et al (2005aDalley et al ( ) (2005b.…”

“…First, it is important to emphasize that there were no group differences in omissions or response latencies in any of the experiments, suggesting that the animals were equally motivated to perform and did not suffer from obvious sensorimotor deficits. In contrast, in studies using the five-choice serial reaction time task, drugtreated animals did show a significant increase in omissions and response latencies, complicating interpretation of the nature of their deficit (Dalley et al, 2005a(Dalley et al, , 2005b. In addition, after the initial withdrawal period LgA animals' signal trial performance was normal, suggesting that the deficits are not attributable to a failure to retrieve the rules governing the responses in the two types of trials.…”

Chronic nicotine administration improves attention while nicotine withdrawal induces performance deficits in the 5-choice serial reaction time task in rats

“…Interestingly, in the 5-CSRTT impaired attentional accuracy, increased omissions and slower latencies to respond has been observed following repeated withdrawal from self-administered amphetamine (Dalley et al, 2005b), cocaine or heroin (Dalley et al, 2005a). However, attentional performance deficits induced by these drugs of abuse were more pronounced and long-lasting than the deficits induced by nicotine in the present study and in that of (Shoaib and Bizarro, 2005).…”

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

“…Repeated administration of psychostimulants has been shown to model important neurobiological, behavioral, and cognitive aspects of schizophrenia, including a sensitized mesolimbic dopamine system and impairments in attentional performance Goldman-Rakic, 1999, 2003;Castner et al, 2004Castner et al, , 2005Crider et al, 1982;Dalley et al, 2005;Featherstone et al, 2007;Fletcher et al, 2005Fletcher et al, , 2007Kapur, 2003;Martinez et al, 2005;Robinson and Becker, 1986;Russig et al, 2002;Tenn et al, 2003Tenn et al, , 2005. Based on extensive evidence indicating the crucial role of the cortical cholinergic input system for attention Parikh et al, 2007;Sarter et al, 2006Sarter et al, , 2005a, the attentional symptoms of schizophrenia have been proposed to be mediated via abnormalities in the regulation and activity of this neuronal system Raedler et al, 2003Raedler et al, , 2007Sarter et al, 2005b).…”