An analysis of cocaine effects on locomotor activities and heart rate in four inbred mouse strains

Ruth, James A.; Ullman, Elizabeth A.; Collins, Allan C.

doi:10.1016/0091-3057(88)90289-4

Cited by 80 publications

(33 citation statements)

References 20 publications

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“…The higher sympathetic drive in the FVB/n strain of mice may minimize the impact of cocaine on sympathetic responses such as heart rate. Furthermore, this is consistent with profound strain differences in heart rate responses to cocaine that have been previously reported (Ruth et al, 1988).…”

Section: Cocaine Aids and Cardiomyopathysupporting

confidence: 75%

Cocaine Increases Mortality and Cardiac Mass in a Murine Transgenic Model of Acquired Immune Deficiency Syndrome

Sutliff

Haase

Russ

et al. 2003

Laboratory Investigation

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SUMMARY:Cardiac dysfunction in AIDS is an important problem. Cocaine is an epidemic associated with sudden death, cardiac dysfunction, and congestive heart failure. Cocaine use and HIV infection frequently coexist in the same patient, yet the combined impact of both is poorly understood. The present study uses cocaine treatment of an established murine AIDS transgenic model (NL4-3⌬ gag/pol; TG) to define the combined effects of AIDS and cocaine on cardiac pathophysiology. To determine the effects of cocaine and HIV-1 proteins on mortality, wild-type and NL4-3⌬ gag/pol mice received saline or cocaine via continuous infusion by Alzet osmotic pumps for 28 days (chronic). Acute cocaine administration (10 days; 40 mg/kg/day) was used to study the nonlethal effects of cocaine in TGs. Echocardiograms and single time point electrocardiograms were performed at the termination of each experiment. Hearts were removed and examined histopathologically. Chronic cocaine treatment (80 mg/kg/day; 28 days) markedly decreased median survival in both wild-type and TG; however, TG survival was significantly more decreased. In acute studies, TG echocardiographic changes included increased left ventricular mass and increased left ventricular fractional shortening compared with all cohorts. Electrocardiographic changes were absent among the groups. Histopathologically, perivascular fibrosis and interstitial fibrosis were evident in cocaine-treated TG. Data suggest that additive cardiac insults (from AIDS and cocaine) result in combined deleterious effects. (Lab Invest 2003, 83:983-989). C ocaine may contribute to the development of cardiomyopathy (CM) in AIDS as a toxin to myocardial cells or through indirect mechanisms based on cocaine's vascular effects and secondary myocardial changes. Accordingly, cardiac effects of cocaine may be a comorbid condition in AIDS CM and vice versa.Cocaine is rapidly cleared and distributed to heart, brain, spinal cord, and other tissues (Inaba et al, 1978;Som et al, 1994;Volkow et al, 1992). Excellent data regarding CM in chronic cocaine administration in humans comes from heart transplantation studies (Karch and Billingham, 1988). Morphologic features in native hearts from chronic cocaine abusers who underwent heart transplantation differed from those seen in non-cocaine abusers.The purpose of our experiments was to address the individual, additive, or synergistic deleterious effects of cocaine and AIDS on the development of cardiac structural and functional abnormalities. We used an established AIDS transgenic model [NL4-3⌬ gag/pol (TG); reviewed in Klotman and Notkins, 1996] that we have used in the past to study CM in AIDS . Mice received continuous cocaine infusion via miniosmotic pumps for 10 days (acute) and 28 days (chronic). Treatment with high-dose cocaine decreased survival in chronic studies. Cocaine-treated TGs develop pathologic lesions including vascular and interstitial fibrosis. Functionally, left ventricular (LV) mass and LV fractional shortening increased in TGs treated with cocaine....

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Section: Cocaine Aids and Cardiomyopathysupporting

confidence: 75%

Cocaine Increases Mortality and Cardiac Mass in a Murine Transgenic Model of Acquired Immune Deficiency Syndrome

Sutliff

Haase

Russ

et al. 2003

Laboratory Investigation

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“…Interestingly, BALB/cByJ mice are more sensitive than other strains to the stimulant effects of low doses of cocaine, but dose-related increases in activity are not observed (Schuster et al 1977;Ruth et al 1988;Reith and Selmeci 1992;Elmer et al 1996;Deroche et al 1997). This strain also shows enhanced response to the cellular or behavioral effects of a variety of stressors (see introductory remarks).…”

Section: Intravenous Cocaine Self-administration In Balb/cbyjmentioning

confidence: 97%

“…This observation cannot be accounted for by pharmacokinetic differences (Ruth et al 1988), capacity to learn operant tasks (Cazala 1976;Deroche et al 1997;Heyser et al 1997), or sensitivity to disruption of operant responding by acute cocaine . However, BALB/cByJ mice have long been considered to be among the inbred strains showing high emotional reactivity, and BALB/cByJ neophobia has been proposed as a model of trait anxiety (Belzung and Berton 1997).…”

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confidence: 99%

Anxiogenic-Like Effects Limit Rewarding Effects of Cocaine in BALB/cByJ Mice

David

Gold

Koob

et al. 2001

Neuropsychopharmacology

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Previous studies have reported intravenous cocaine selfadministration behavior in several strains of mice with the exception of BALB/cByJ, a strain considered a mouse model of high emotional reactivity. The present experiments further investigated acquisition of self-administration in BALB/cByJ mice using a low dose and a habituation session. Following evidence of an initial drug-seeking behavior, we observed a progressive decline of intravenous self-administration. Pretreatment with diazepam (0.5 mg/ kg, IP), reinstated cocaine-maintained responding. To test the hypothesis that injections directly into a rewardrelevant brain region might support consistent cocaineseeking behavior, BALB/cByJ mice implanted in the nucleus accumbens (NAc) or the caudate-putamen nucleus (CPu) were trained to discriminate between the arm enabling a microinjection of cocaine (30 pmol/50 nl or 150 pmol/50 nl) The reinforcing effect of cocaine has long been demonstrated in several species including humans, (Pickens and Thompson 1968;Woods and Schuster 1968;Deneau et al. 1969;Goldberg 1973;Fischman and Schuster 1982). However, in studies using monkeys as well as rats, not all individual subjects exhibit acquisition of self-administration, and data from subjects that fail to acquire selfadministration are usually excluded (Davis and Smith 1987). Consistent with these observations, many humans experiencing psychostimulant drugs do not develop compulsive drug-seeking behavior (Siegel 1984;O'Brien et al. 1986). Recently, an increasing number of studies have investigated the biological basis of the vulnerability to drug abuse in outbred rats. From this work, it is possible to define a vulnerability profile based on a number of behavioral, neurochemical, and endocrinological features (Hooks et al. 1991;Piazza and Le Moal 1996). Importantly, traits associated with a vulnerable phenotype in rats, such as novelty-induced activity, can be compared to psychological dimensions measured in humans, such as novelty-seeking behavior (see Bardo et al. 1996). It is of special interest to note here that novelty- Cocaine Self-Administration in BALB/cByJ Mice 301 seeking and drug-seeking behaviors co-vary in humans as well as laboratory animals (Bardo et al. 1996). These behaviors are also expressed differentially in inbred strains of mice making these mice a potentially important model for further examining the relationship between behavioral traits, their underlying biological basis, and drug-seeking behavior (Crabbe et al. 1994).Of particular interest in this context is the difficulty of demonstrating intravenous cocaine self-administration in BALB/cByJ mice (Deroche et al. 1997;Roberts et al. 1997;Yu et al. 1997), using doses known to maintain self-administration in C57BL/6 or several other strains (Carney et al. 1991;Grahame et al. 1995;Deroche et al. 1997;Rocha et al. 1998). This observation cannot be accounted for by pharmacokinetic differences (Ruth et al. 1988), capacity to learn operant tasks (Cazala 1976;Deroche et al. 1997;Heyser et al. 199...

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“…cocaine self-administration behavior (Piazza et al, 2000). Likewise, inbred mice strains differ significantly in cocaine-induced locomotor activity, but not in brain cocaine levels (Ruth et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Individual Differences in Cocaine-induced Locomotor Activity in Rats: Behavioral Characteristics, Cocaine Pharmacokinetics, and the Dopamine Transporter

Gulley

Hoover

Larson

et al. 2003

Neuropsychopharmacol

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Outbred male Sprague-Dawley rats can be classified as either low or high cocaine responders (LCRs or HCRs, respectively) based on their locomotor response to acute cocaine. Concomitant measurement of dopamine clearance in these rats revealed that the differential behavioral responses are associated with the magnitude of dopamine transporter (DAT) inhibition by cocaine. Here, we investigated several factors that might contribute to cocaine-induced behavioral variability and its association with differential inhibition of DAT function. In rats classified as LCRs or HCRs after 10 mg/kg cocaine injection, we found no differences in (1) novelty-induced locomotion, (2) cocaine levels in dorsal striatum or nucleus accumbens (NAc), (3) DAT number or affinity in NAc, or (4) DAT affinity for cocaine in NAc. In rats given 20 mg/kg cocaine, behavior was more uniform across individuals, but still warranted separation into LCR/HCR categories. Additionally, we analyzed the stability of the LCR/HCR classification made during the first test with 10 or 20 mg/kg cocaine by retesting rats 7 days later with saline or cocaine (10 or 20 mg/kg). Before injection, HCRs were more active relative to LCRs and to their own behavior on the first test day. Following cocaine, LCRs and HCRs exhibited similar drug-induced changes in locomotion, but there were unique effects that depended on the cocaine dose given on the first and second test days. Our results argue against several likely explanations for individual differences in cocaine-induced behavior and highlight the influence of a single cocaine exposure on subsequent behavioral responses to the drug.

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An analysis of cocaine effects on locomotor activities and heart rate in four inbred mouse strains

Cited by 80 publications

References 20 publications

Cocaine Increases Mortality and Cardiac Mass in a Murine Transgenic Model of Acquired Immune Deficiency Syndrome

Cocaine Increases Mortality and Cardiac Mass in a Murine Transgenic Model of Acquired Immune Deficiency Syndrome

Anxiogenic-Like Effects Limit Rewarding Effects of Cocaine in BALB/cByJ Mice

Individual Differences in Cocaine-induced Locomotor Activity in Rats: Behavioral Characteristics, Cocaine Pharmacokinetics, and the Dopamine Transporter

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