Prolonged Behavioral Effects of in Utero Exposure to Lead or Methyl Mercury: Reduced Sensitivity to Changes in Reinforcement Contingencies during Behavioral Transitions and in Steady State

Newland, M. Christopher; Sheng, Yuchen; Lögdberg, Bengt; Berlin, Maya

doi:10.1006/taap.1994.1084

Cited by 76 publications

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“…It is noteworthy, in light of this possibility, that in several cases behavior was reestablished by placing the rat under a less demanding DRH schedule and thereby increasing the reinforcement density, a sort of behavior therapy (for a related application, see Ref. [29]). …”

Section: Discussionmentioning

confidence: 99%

Aging unmasks adverse effects of gestational exposure to methylmercury in rats

Newland

Rasmussen

2000

Neurotoxicology and Teratology

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The consequences of developmental exposure to methylmercury on behavior in aged animals were investigated. Methylmercury exposure was arranged by placing 0, 0.5 or 6.4 ppm Hg in the drinking water of female rats at least 4 weeks before mating and continuing until postnatal (PN) day 16. Brain Hg concentrations in cohorts of low-and high-dose offspring were 0.5 and 9.1 ppm at birth and 0.04 and 0.52 ppm at weaning (described in another report). Lever pressing of female offspring was maintained under a Multiple Differential Reinforcement of High Rate 9:4 Extinction schedule of food reinforcement (Mult DRH 9:4 EXT). Under the DRH 9:4 schedule, a food reinforcer was delivered when nine responses occurred within 4 s. Under the Extinction schedule, responding had no programmed consequences. No exposure-related differences in reinforcement rate under the DRH schedule or discrimination between the DRH and extinction components were apparent initially. At 950 days of age, the overall response rates of controls had shown a gradual decline over the previous 500 days to about 80% of their beginning levels, but, otherwise, most controls were healthy. A gradual decline in the reinforcement rate began to appear in low-and high-dose rats at about 500 and 800 days of age, respectively. Microanalyses of the nine-response burst maintained by the DRH schedule revealed that the lever-press duration increased, the inter-response time (IRT) was unaffected, and the time between response bursts increased. Overall, the nine-response burst remained intact as a coherent response unit. The increased time between response bursts caused the decline in reinforcement rate. All rats displayed these effects as they aged, but the mercury-exposed rats did so sooner. D 2000 Elsevier Science Inc. All rights reserved.The hypothesis of``silent damage'' holds that neurotoxicants can act in undetectable ways until another event, such as aging, further challenges nervous system function [38,39]. Difficulties in detecting such damage could be due to the nervous system's extraordinary compensatory ability or because the threshold for neural damage has not been crossed. Delayed neurotoxicity, a necessary element of the hypothesis, is clearly established with methylmercury, especially in sensory± motor domains [4,10,32].In reports that may have prompted the original hypothesis, mice exposed during gestation to high levels of methylmercury showed progressive deterioration in swimming ability and other motor endpoints as they aged [34 ± 36]. These early reports have been supplemented by more recent studies with nonhuman primates [32]. In these, sensory ± motor function [31,32] and higher-order visual function [33] deteriorated more in aging monkeys that had been exposed during development to methylmercury than in controls.Support for the hypothesis that silent damage becomes apparent with aging is also accruing from long-term studies of individuals exposed to methylmercury. As people exposed to methylmercury during the Minamata tragedy have aged, activi...

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Section: Discussionmentioning

confidence: 99%

Aging unmasks adverse effects of gestational exposure to methylmercury in rats

Newland

Rasmussen

2000

Neurotoxicology and Teratology

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“…Included among these effects are impaired sensory function in nonhuman primates (Rice, 1996;Gilbert, 1982, 1990), retarded behavior in transition in rodents and nonhuman primates (Newland et al, 2004;Newland et al, 1994;Paletz et al, 2006), deficits in complex, high-rate operant behavior (Newland and Rasmussen, 2000), disrupted performance on timing in fixed-interval schedules of reinforcement (Rice, 1992), delayed object permanence (Burbacher et al, 1988;Gunderson et al, 1988b), and impaired facial recognition (Gunderson et al, 1988a). Performance on tasks that tap memory function, however, are relatively spared after developmental MeHg exposure (Elsner et al, 1988;Gilbert et al, 1993;Goldey et al, 1994;Newland and Paletz, 2000).…”

Section: Introductionmentioning

confidence: 99%

Spatial and visual discrimination reversals in adult and geriatric rats exposed during gestation to methylmercury and n−3 polyunsaturated fatty acids

et al. 2007

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Fish contain essential long chain polyunsaturated fatty acids (PUFAs), particularly docosahexaenoic acid (DHA), an omega-3 (or n-3) PUFA, but are also the main source of exposure to methylmercury (MeHg), a potent developmental neurotoxicant. Since n-3 PUFAs support neural development and function, benefits deriving from a diet rich in n-3s have been hypothesized to protect against deleterious effects of gestational MeHg exposure. To determine whether protection occurs at the behavioral level, female Long-Evans rats were exposed, in utero, to 0, 0.5, or 5 ppm of Hg as MeHg via drinking water, approximating exposures of 0, 40, and 400 μg Hg/kg/day and producing 0, 0.29, and 5.50 ppm of total Hg in the brains of siblings at birth. They also received pre-and postnatal exposure to one of two diets, both based on the AIN-93 semipurified formulation. A "fish-oil" diet was high in, and a "coconut-oil" diet was devoid of, DHA. Diets were approximately equal in α-linolenic acid and n-6 PUFAs. As adults, the rats were first assessed with a spatial discrimination reversal (SDR) procedure and later with a visual (nonspatial) discrimination reversal (VDR) procedure. MeHg increased the number of errors to criterion for both SDR and VDR during the first reversal, but effects were smaller or nonexistent on the original discrimination and on later reversals. No such MeHg-related deficits were seen when the rats were retested on SDR after two years of age. These results are consistent with previous reports and hypotheses that gestational MeHg exposure produces perseverative responding. No interactions between Diet and MeHg were found, suggesting that n-3 PUFAs do not guard against these behavioral effects. Brain Hg concentrations did not differ between the diets, either. In geriatric rats, failures to respond were less common and response latencies were shorter for rats fed the fish oil diet, suggesting that exposure to a diet rich in n-3s may lessen the impact of age-related declines in response initiation.

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“…Disruption of reinforcement processes in the form of impaired sensitivity to changes in reinforcement contingencies has significant implications. Sensitivity to consequences, and specifically to reinforcer frequency, is a critical process in adaptive behavior (Newland et al 1994;Staddon 1998). Individuals able to efficiently modify behavior patterns in accord with changes in environmental contingencies are conferred a decided advantage over potential competitors (Skinner 1984).…”

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confidence: 99%

Marijuana Effects on Sensitivity to Reinforcement in Humans

Lane

Cherek

2002

Neuropsychopharmacology

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Administration of marijuana has consistently been shown to disrupt behavioral and CNS functions, including acquisition and choice discrimination learning, short-term memory, and time perception (Adams and Barratt 1976;Chait and Pierri 1992;Darley et al. 1973;Heishman et al. 1990;Kelly et al. 1993;Schulze et al. 1989;Vachon et al. 1974). These acute effects-which are evident in rats, monkeys, and humans-are presumably related to the disruptive action of ⌬ 9 THC in the brain. With regard to learning processes, some laboratory tasks like repeated acquisition and match to sample are shaped and maintained by reinforcement, e.g., food, money, or positive feedback (Kelly et al. 1993;Schulze et al. 1989). However, studies of acute marijuana effects on reinforcement-based learning have focused on the acquisition of response patterns rather than sensitivity to reinforcer frequency or magnitude, and less is known about the interaction between acute marijuana intoxication and behavioral sensitivity to reinforcement frequency.Two questions logically precede an inquiry into the effects of marijuana on sensitivity to reinforcement. Why would one expect any relationship? Why would such a relationship be important? At the behavioral level, acute administration of ⌬ 9 THC has repeatedly been shown to impair performance on learning tasks shaped and maintained by reinforcement Balster 1980, Kelly et al. 1993;Kamien et al. 1994;Schulze et al. 1989). Furthermore, on simulated tasks in which subjects could work to earn money, acute marijuana smoking decreased rates of working (and earnings)-an effect presumably mediated by changes in From the Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center -Houston.Address correspondence to: Scott D. Lane, Ph.D., Dept of Psychiatry and Behavioral Sciences, UTSHC-Houston, 1300 Moursund St., Houston, TX 77030, Tel.: (713) 500-2620, Fax: (713) NO . 4 Marijuana and Sensitivity to Reinforcement 521 reinforcement or "motivational" processes (Foltin et al. 1989;Haney et al. 1997, Kagel et al. 1980Miles et al. 1974;Pihl and Sigal 1978). While the present study was not intended to address specific mechanisms, activity at the biochemical level provides a plausible rationale for disruptive effects of ⌬ 9 THC on reinforcement processes. Marijuana impacts both dopamine (DA) and cannabinoid (CB) receptor systems. Administration of ⌬ 9 THC modifies DA release in the "reward pathway", or mesolimbic DA system, projecting from the ventral tegmental area to the nucleus accumbens and into prefrontal cortex (Chen et al. 1990, Gardner and Lowinson 1991, Tanda et al. 1997. Since this pathway is a primary site involved in reinforcement processes (Fibiger and Phillips 1988;Koob and Swerdlow 1988;Wise and Rompre 1989), it follows that marijuana may have acute effects on behavioral sensitivity to reinforcement (see also Loeber and Yurgelun-Todd 1999). ⌬ 9 THC also directly modifies CB receptor function, including sites in the amygdala and hippocampus (Herkenham 1995;Heyser e...

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Prolonged Behavioral Effects of in Utero Exposure to Lead or Methyl Mercury: Reduced Sensitivity to Changes in Reinforcement Contingencies during Behavioral Transitions and in Steady State

Cited by 76 publications

References 0 publications

Aging unmasks adverse effects of gestational exposure to methylmercury in rats

Aging unmasks adverse effects of gestational exposure to methylmercury in rats

Spatial and visual discrimination reversals in adult and geriatric rats exposed during gestation to methylmercury and n−3 polyunsaturated fatty acids

Marijuana Effects on Sensitivity to Reinforcement in Humans

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