Effects of isradipine on cocaine-induced changes in cognitive performance in recently abstinent cocaine-dependent individuals

Abstract

Recently abstinent cocaine-dependent individuals, compared with healthy controls, appear more likely to exhibit deficits in cognitive performance and attention. Individuals with such cognitive deficits might be less able to avail themselves of rehabilitative or relapse-prevention efforts. Pharmacotherapy that reduces the impairment in cognitive performance among cocaine-dependent individuals would be a useful clinical tool. Preclinical and human studies suggest that the dihydropyridine-class calcium-channel antagonist, isradipine, can enhance neurocognitive function in some neuropsychiatric disorders. Isradipine, presumably by increasing cerebral blood flow and its actions at various neurotransmitter systems, might, therefore, ameliorate the impairment in cognitive performance and attention seen in cocaine addicts and enhance the expected modest improvement in performance during acute cocaine-taking in these same individuals. Among 12 male and female cocaine-dependent individuals, we examined the effects of low and high doses of intravenous cocaine (0, 0.325, and 0.650 mg/kg) on cognitive performance and attention in both the presence and absence of isradipine (0 or 30 mg sustained release each evening prior to testing, plus 0 or 15 mg immediate release each morning 2 h before the cocaine or placebo cocaine infusion and on the day of testing). Intravenous cocaine produced a modest increase in cognitive performance and attention. Isradipine, both with and without cocaine, had no effect on these same parameters. Hence, cocaine-taking by cocaine-dependent individuals produces little improvement in cognitive performance and attention in either the presence or absence of isradipine.

The Neuropsychology of Cocaine Addiction: Recent Cocaine Use Masks Impairment

“…Consistent with the more frequent and recent cocaine use in the CUD + group, this pattern of results may be attributed to the neurocognitive enhancing effects of acute cocaine in CUD (Higgins et al, 1990;Johnson et al, 1998Johnson et al, , 2005, discussed below. Figure 1 Neuropsychological performance of cocaine-addicted subjects as compared with control subjects.…”

“…These NP deficits encompassed attention/ executive function and verbal learning and memory, and could not be attributed to measures that frequently vary between healthy control and cocaine-addicted individuals (eg, dysphoria and cigarette smoking, and also socioeconomic status and general intellectual functioning). As these impairments were most accentuated in the CUDÀ subgroup, it may be speculated that the relatively better cognitive functioning in the CUD + subgroup reflects the mild cognitive improvement with active cocaine use (Johnson et al, 2005) that may potentially predispose to relapse. This speculation emphasizes the importance of developing or using a pharmacological agent that could improve neurocognitive function without negatively impacting mood thereby increasing positive outcome in treatment trials.…”

L‐type calcium channels and psychiatric disorders: A brief review

“…As summarized in Table III, conflicting results have been reported in preliminary clinical studies examining stimulants' abuse liability in humans [Muntaner et al, 1991;Rosse et al, 1994;Fabian and Silverstone, 1997;Johnson et al, 1999Johnson et al, , 2004Johnson et al, , 2005bMalcolm et al, 1999;Gottschalk and Kosten, 2002;Sofuoglu et al, 2003;Roache et al, 2005]. Roache et al [2005] suggested that isradipine could even increase subjective effects and reinforcement caused by cocaine use.…”

ΔFosB Induction in Orbitofrontal Cortex Mediates Tolerance to Cocaine-Induced Cognitive Dysfunction

“…Cognitive deficits associated with withdrawal from long-term cocaine use have been attributed to OFC dysfunction (Schoenbaum et al, 2006). However, recent findings indicate that the cognitive abilities of cocaine addicts are either improved or unaffected by acute cocaine (Hopper et al, 2004;Johnson et al, 2005), and data from preclinical studies indicate that chronic amphetamine intake reduces the impulsive responding caused by an acute dose of the drug (Dalley et al, 2005b). Chronic psychostimulant exposure therefore appears to reduce the susceptibility of individuals to the cognitive dysfunction caused by the drug, yet this tolerance is accompanied by impairments in cognition after cessation of drug use.…”