Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

Abstract

McBride SM, Culver B, Flynn FW. Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines. Am J Physiol Regul Integr Comp Physiol 295: R899 -R905, 2008. First published July 9, 2008 doi:10.1152/ajpregu.00186.2008This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n ϭ 6 -8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low-and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors. behavioral sensitization; psychomotor stimulant; salt appetite DRUGS OF ABUSE and natural motivators or stimuli, such as sodium deprivation or stress, activate similar neural circuits involved in mediating reward and drive-related responses (12,18,28). One of the main systems believed to be involved in triggering these behaviors is the mesocorticolimbic dopamine system, with dopaminergic projections traveling from the midbrain ventral tegmental area to the nucleus accumbens and other limbic and cortical areas (38, 44). With repeated exposure to both amphetamines and sodium deprivation, behavioral sensitization develops (38, 48). Sensitization can be described as an increased and enduring response to the same stimuli with repeated exposures (38). With amphetamines, sensitization manifests itself as increased locomotor behavior (21, 53). Repeated amphetamine treatment leading to sensitization is associated with morphological changes in nucleus accumbens neurons, including increased spine density, dendritic length, and dendritic branching (46). Repeated sodium deprivation can lead to an enduring daily increase in the ingestion of hypertonic NaCl in otherwise sodium-replete rats (48), and a history of sodium deple...

High‐Salt Exposure During Perinatal Development Enhances Stress Sensitivity

“…The primary aim of our study was to expand upon previous work by our colleagues that showed perinatal high‐salt exposure facilitated physiological adaptations to stress (McBride et al, ). In our structural analysis of weanling and adult rats, we observed an increase in spine density in the NAc‐Sh (Fig.…”

“…B). This was curious given the previous reports that early high‐salt exposure increases the locomotor response to amphetamine (McBride et al, ) and that sodium appetite and cocaine‐induced locomotor behavior cross‐sensitize (Acerbo and Johnson, ). The CPP model however assesses a preference for drug‐associated environments rather than the mere physiological response to a drug.…”

“…In addition to physiological parameters, early excess salt exposure has been shown to augment behavioral responsiveness to both natural and drug rewards. Specifically, adult offspring born to high‐salt fed dams display an enhanced preference for salt (Contreras, ; McBride et al, ) and glucose solutions (Contreras, ) as well as a heightened locomotor response to amphetamine (McBride et al, ). These observations suggest that perinatal salt exposure may serve as an early life stressor, predisposing offspring to diseases of reward dysregulation, much like other forms of stress increase vulnerability to drug use and addiction (Sinha, ).…”

“…Specifically, adult offspring from high‐salt fed dams, using the model described above, display increased basal corticosterone (CORT) levels compared to controls (Gray et al, ). When maternal salt consumption is limited to the prenatal period only, offspring no longer exhibit heightened basal CORT levels but do demonstrate a relatively elevated CORT and adrenocorticotropic response to acute stress (McBride et al, ) as well as an increase in corticotrophin‐releasing hormone mRNA levels in the paraventricular nucleus under both basal and stress‐induced conditions (Porter et al, ). In addition to physiological parameters, early excess salt exposure has been shown to augment behavioral responsiveness to both natural and drug rewards.…”

Maternal High-Salt Intake During Pregnancy Reprogrammed Renin–Angiotensin System-Mediated Cardiomyocyte Apoptosis in the Adult Offspring Heart

“…9 Exposure to excess salt during early developmental periods may cause long-term physiological changes in later life in rats. 10 Following in utero exposure to high salt (HS), the offspring showed a suppressed renin-angiotensin system (RAS), indicating HS diet during pregnancy may reprogram RAS. 11,12 These may produce offspring with maladaptive phenotypes in a predicted adult life.…”