Methamphetamine exposure during early postnatal development in rats: II. Hypoactivity and altered responses to pharmacological challenge

Vorhees, Charles V.; Ahrens, Katja; Acuff‐Smith, Karen D.; Schilling, Mary A.; Fisher, J. Edward

doi:10.1007/bf02249329

Cited by 51 publications

(24 citation statements)

References 24 publications

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“…These results suggest that dopaminergic system plays an important role in the phenotype of several behaviors, especially excess dopaminergic activation was involved in the combined effects of methamphetamine and morphine on the locomotor activity in mice. These findings may explain why high doses (e.g., 20 mg / kg) of methamphetamine decrease the locomotor activity in rodents (35,36, and present results). Although, the present study was not designed to investigate the vertical effect (e.g., rearing), methamphetamine and cocaine-induced rearing was almost completely abolished when combined with morphine.…”

Section: Discussionsupporting

confidence: 71%

Combined Effects of Psychostimulants and Morphine on Locomotor Activity in Mice

et al. 2004

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Abstract. Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. This combination appears to produce synergistic effects on behavior at low doses; however, there is little direct evidence that the combination is stronger than either drug alone. Therefore, we investigated interactions between psychostimulants and morphine on locomotor activity in mice. Low doses of cocaine (5.0 mg / kg) or methamphetamine (0.5 mg/ kg) and morphine (10 mg / kg) enhance locomotor activity in a synergistic fashion. Effective doses of cocaine (20 mg / kg) and morphine (20 mg / kg) increased locomotion in an additive fashion. In contrast, combination of methamphetamine (1.0 and 2.0 mg / kg) and morphine (10 and 20 mg / kg) did not merely enhance their effects (or attenuated the peak effects of methamphetamine-induced hyperlocomotion). These results indicate that different mechanisms explain the interaction between morphine and methamphetamine or cocaine. It is well known that psychostimulants-and opioids-induced hyperlocomotion is mediated by the activation of the dopaminergic system, however, haloperidol (a dopamine receptor antagonist) and U50,488H (which attenuates dopamine release from nerve terminals) significantly increased the effects of methamphetamine and morphine on the locomotor activity. These results suggest that excess dopaminergic activation may be involved in the effects of methamphetamine and morphine on locomotor activity in mice.

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Section: Discussionsupporting

confidence: 71%

Combined Effects of Psychostimulants and Morphine on Locomotor Activity in Mice

et al. 2004

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“…More striking than this is the effect MA exposure had on the development of learning in the Morris hidden platform maze. As can be seen in Figure 12, the later-exposed group showed a significant delay both in initial learning and in learning a new goal position when the platform was shifted to another location (26,27 …”

Section: The Drugs and Their Actions Phenytoimentioning

confidence: 87%

“…However, when these same offspring were tested on a complex water maze, they showed no learning deficits. By comparison, rats exposed later in development to d-MA also exhibited heightened startle ( Figure 10) and they committed more errors in a complex water maze ( Figure 11) (26,27).…”

Section: The Drugs and Their Actions Phenytoimentioning

confidence: 99%

Developmental neurotoxicity induced by therapeutic and illicit drugs.

Vorhees¹

1994

Environ Health Perspect

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The developmental neurotoxicity of phenytoin, isotretinoin, and methamphetamine has been reviewed to illustrate effects from both therapeutic and illicit drugs to which people are exposed and which either induce or show the potential for inducing learning disabilities following in utero exposure. In each case both human and experimental animal data are presented and compared where possible. The findings point to several conclusions. First, some drugs in current use induce developmental neurotoxicity, and it cannot safely be assumed that there are not more as yet unidentified. Second, of the types of neurotoxicity induced by drugs, learning disabilities figure prominently. Third, the effects observed are dependent on both the drug's mechanism of action and the period of brain development during which exposure occurs. Fourth, with the exception of CNS teratogens, it is not yet possible to predict which periods of brain development are the most vulnerable for the induction of learning disabilities, as seen by the different patterns of critical periods for phenytoin and isotretinoin compared to methamphetamine. Fifth, as seen with isotretinoin, existing drugs that cause developmental neurotoxicity are not the only problem; new drugs with such effects are still being introduced. Sixth, only a small fraction of the drugs currently in use have ever been examined for developmental neurotoxicity; hence, the full scope of the problem cannot even be accurately estimated based on current information. It is concluded that prevention of new cases caused by drugs such as isotretinoin should be a high priority for future regulatory action. -Environ Health Perspect 102(Suppl 2): 145-153 (1994).

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“…Methamphetamine administration during early postnatal development in rats results in impaired learning in a T-maze if administration occurs from postnatal Days 1 to 10, and impaired learning in the Morris water maze if administration occurs from postnatal Days 11 to 20 (Vorhees, Ahrens, Acuff-Smith, Schilling, & Fisher, 1994a). These same rat pups also were hypoactive, with the greatest reduction in activity occurring at 30 days of age, although some males continued to show reduced activity at 45 and 60 days of age (Vorhees, Ahrens, Acuff-Smith, Schilling, & Fisher, 1994b).…”

Section: Introductionmentioning

confidence: 87%

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice

McFadyen

Brown

Carrey³

2002

Developmental Psychobiology

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Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a treatment for children with attention deficit hyperactivity disorder (ADHD), yet little research has been conducted to determine its potential long-term neurobehavioral effects. We assessed the effects of subchronic MPH administration (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD-1 mice treated from 26 to 32 days of age. When tested at 33 days of age in the open field and elevated plus maze, there were no significant differences in spontaneous locomotion, exploration, or fear- and anxiety-related behaviors. Testing from 34 to 37 days of age in a water maze task revealed no significant effects of any dose of MPH on learning in this simple paradigm. While it is difficult to extrapolate directly from these results to clinical effects in humans, our results indicate that preexposure of mice to MPH late in the postnatal developmental period does not appear to alter later behavior. We are currently conducting additional studies to further probe the potential effects of MPH administration during development and to examine various contributing factors including stage of development, duration of MPH administration, complexity of the task used to assess behavioral changes, and type of cognitive process being analyzed (attention, nonspatial working memory, etc.).

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Methamphetamine exposure during early postnatal development in rats: II. Hypoactivity and altered responses to pharmacological challenge

Cited by 51 publications

References 24 publications

Combined Effects of Psychostimulants and Morphine on Locomotor Activity in Mice

Combined Effects of Psychostimulants and Morphine on Locomotor Activity in Mice

Developmental neurotoxicity induced by therapeutic and illicit drugs.

Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice

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