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

Abstract

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.

Adolescent methylmercury exposure affects choice and delay discounting in mice

“…Because magnitude-sensitivity estimates decreased due to MeHg exposure in the current study, this would suggest increased responding on the smaller-reinforcer lever in exposed mice. Gestational MeHg exposure increases perseverative errors (i.e., enhances responding on a previously reinforced lever) in spatial- and visual-discrimination reversals in rats (Paletz et al, 2007; Reed et al, 2006). In this account, the impact of adolescent MeHg exposure would resemble that of gestational exposure, though a systematic investigation of the effects of adolescent MeHg exposure on reversal learning would be necessary.…”

“…Exposure to low doses of MeHg during gestation presents a particular concern because of the development of brain neurocircuitry during this period (Choi, 1991; Rice & Barone, 2000). In laboratory models, gestational MeHg exposure impairs the acquisition of choice (Newland, Reile, & Langston, 2004; Newland, Yezhou, Logdberg, & Berlin, 1994) and spatial- and visual-discrimination reversals (Paletz, Day, Craig-Schmidt, & Newland, 2007; Reed, Paletz, & Newland, 2006). MeHg-induced alterations to the dopamine neurotransmitter system are thought to underlie these behavioral impairments (Newland, Reed, & Rasmussen, 2015).…”

A bout analysis reveals age-related methylmercury neurotoxicity and nimodipine neuroprotection

“…The autoshaping procedure has been described in detail previously [see 49 and 50] and was implemented without modification for both age groups. Autoshaping sessions ended when animals met a specific response criterion or after 4hr whichever occurred first.…”

Spatial discrimination reversal and incremental repeated acquisition in adolescent and adult BALB/c mice

“…The autoshaping procedure has been described in detail previously (see Reed et al, 2006; Paletz et al, 2007) and was implemented without modification with the adolescents and adults. Generally, adults completed one autoshaping session per day (training on one lever).…”

“…Discrimination reversal procedures have been used in humans and a range of non-human animals (Fellows & Farah, 2003; Pagani et al, 2004) and are sensitive to disruption of the orbitofrontal cortex in rodents, nonhuman primates, and humans (Dalley et al, 2004; Zald & Andreotti, 2010). The first reversal is especially sensitive to disruption of the orbitofrontal cortex by lesions, by altering neurotransmitter (especially dopamine) activity in this region (Dalley et al, 2004), and by gestational methylmercury (MeHg) exposure in rodents (Paletz et al, 2007; Reed et al, 2006). SDR procedures present an opportunity to examine behavioral flexibility in adolescent mammals, a period marked by transient dopaminergic (DAergic) functioning and structural development.…”