Periodic postpartum separation from the offspring results in long-lasting changes in anxiety-related behaviors and sensitivity to morphine in Long-Evans mother rats

Kalinichev, Mikhail; Easterling, Keith W; Holtzman, Stephen G.

doi:10.1007/s002130000556

Cited by 43 publications

(61 citation statements)

References 71 publications

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“…Two of these measures and associated behaviors were horizontal activity counts (ambulation) and vertical activity counts (rearing). In addition, the ratio of center distance to total distance traveled was analyzed as an index of emotional reactivity (Crawley, 1999;Harro, 1993;Kalinichev et al, 2000).…”

Section: Locomotor Activity Testingmentioning

confidence: 99%

“…Movements were determined by breaks in an array of 48 photobeams (24 × 24; 6 cm apart). The general testing procedure has been described elsewhere in rats (Kalinichev et al, 2000) and mice (Holmes et al, 2000). Briefly, each mouse was placed in the plus-maze, facing a closed arm, and was allowed to explore freely the plus-maze for 10 min.…”

Section: Elevated Plus-mazementioning

confidence: 99%

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Learning and memory deficits in mice lacking protease activated receptor-1

Almonte

Hamill

Chhatwal

et al. 2007

Neurobiology of Learning and Memory

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The roles of serine proteases and protease activated receptors have been extensively studied in coagulation, wound healing, inflammation, and neurodegeneration. More recently, serine proteases have been suggested to influence synaptic plasticity. In this context, we examined the role of protease activated receptor 1 (PAR1), which is activated following proteolytic cleavage by thrombin and plasmin, in emotionally-motivated learning. We were particularly interested in PAR1 because its activation enhances the function of NMDA receptors, which are required for some forms of synaptic plasticity. We examined several baseline behavioral measures, including locomotor activity, expression of anxiety-like behavior, motor task acquisition, nociceptive responses, and startle responses in C57Bl/6 mice in which the PAR1 receptor has been genetically deleted. In addition, we evaluated learning and memory in these mice using two memory tasks, passive avoidance and cued fear-conditioning. Whereas locomotion, pain response, startle, and measures of baseline anxiety were largely unaffected by PAR1 removal, PAR1−/− animals showed significant deficits in a passive avoidance task and in cued fear conditioning. These data suggest that PAR1 may play an important role in emotionally-motivated learning.

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Section: Locomotor Activity Testingmentioning

confidence: 99%

Section: Elevated Plus-mazementioning

confidence: 99%

Learning and memory deficits in mice lacking protease activated receptor-1

Almonte

Hamill

Chhatwal

et al. 2007

Neurobiology of Learning and Memory

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“…Periodic separations from the offspring alter maternal behavior of the dam, even though the exact nature of this impact is still debated (Lee and Williams, 1974;Liu et al, 1997;Boccia and Pedersen, 2001;Pryce et al, 2001). We provided the first evidence that in the rat, the impact on the dam of periodic separations from the litter is long lasting and involves fear/ anxiety neural networks as well as endogenous opioid systems (Kalinichev et al, 2000). Indeed, the maternal neural system is involved in active 'crosstalk' with the fear/ anxiety-mediating neural system (Fleming et al, 1980(Fleming et al, , 1988(Fleming et al, , 1989Fleming and Luebke, 1981) and is modulated by endogenous opioids (Mayer et al, 1985;Panksepp et al, 1994;Zaias et al, 1996;Nelson and Panksepp, 1998;Byrnes and Bridges, 2000).…”

Section: Introductionmentioning

confidence: 90%

Long-Lasting Changes in Morphine-Induced Locomotor Sensitization and Tolerance in Long-Evans Mother Rats as a Result of Periodic Postpartum Separation from the Litter: A Novel Model of Increased Vulnerability to Drug Abuse?

Kalinichev

Easterling

Holtzman

2002

Neuropsychopharmacol

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Daily postpartum separations from the litter produce enduring changes in anxiety and sensitivity to the antinociceptive effects of morphine in Long-Evans dams. We tested whether postpartum experience alters sensitivity to the effects of morphine on locomotor activity. Dams were tested 4-6 weeks after their pups were weaned, and had one of the following backgrounds: daily separation from the litter on postpartum days 2-14 for either 3 h (prolonged separationFLS) or 15 min (brief separationFBS), or no separation (nonhandled controlFNH). After 2 consecutive days (B1-2) of baseline activity measurements, subjects were tested daily after s.c. injections of either morphine (10 mg/kg) or saline for 7 days and again on day 10. Beginning 5 days later, saline and 1.0-10 mg/kg of morphine were tested in all dams. On B1, LS and BS dams habituated slower than NH controls, yielding higher horizontal counts. LS dams failed to habituate across baseline days and were more active than other dams on B2. Sensitization, a progressive increase in horizontal activity, was more rapid and robust in LS and BS dams compared to NH animals. LS was the only group that developed tolerance to morphine-induced decreases in vertical activity. In LS dams with the history of morphine treatment, injection of saline resulted in higher horizontal activity and center time compared to saline-treated counterparts, indicative of conditioning. Among animals with a history of saline treatment, LS dams were more sensitive to morphine challenges than BS and NH dams. As a result of the robust and long-lasting increases in the ability of morphine to induce behavioral sensitization in litter-separated dams, periodic postpartum separation may represent a new animal model of increased vulnerability to substance abuse.

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“…Although only a 10% sucrose solution was used in constructing the NTX dose response curve, all animals had previously been exposed to all sucrose concentrations, and this may have altered the reinforcing properties of the 10% solution (Taha et al, 2006). It is also possible that the effects of the maternal separation procedure on dams dissipated by the time of experiment 2 (which was conducted 3 weeks after experiment 1), as they are known to dissipate over time (Kalinichev et al, 2000). What experiments could be conducted with the dams was also limited by the small number of subjects available (1 dam/litter) compared to the number of offspring available (10 offspring/litter).…”

Section: Effect Of Naltrexonementioning

confidence: 99%

“…Again rat pups of both sexes were tested in a two-bottle choice procedure, this time following administration of varying doses of naltrexone. Early postnatal stress also affects fluid consumption in the dams of litters that have undergone the maternal separation procedure (Michaels & Holtzman, 2006), and apparently the endogenous opioid system of the dams as well (Kalinichev et al, 2000(Kalinichev et al, ,2002. Therefore, the dams from MS and NH litters were also tested using similar procedures to their offspring.…”

Section: Introductionmentioning

confidence: 99%

Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake and sucrose consumption in maternally separated rats

Michaels

Holtzman

2007

Pharmacology Biochemistry and Behavior

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Early-life stress has been identified as a risk factor in the development of a host of disorders, including substance abuse; however the link between early postnatal stress and changes in measures of reward has not been thoroughly researched. The current study had two main objectives: 1) to determine the impact of maternal separation (an animal model of early-life stress) on the consumption of 10% and 2.5% sucrose solutions by Long-Evans rat dams and male and female offspring, and 2) to determine the effect of the opioid antagonist naltrexone (0.1 -3.0 mg/kg) on drinking by each of those groups. Dam-pup separations occurred for varying lengths of time during the first two postnatal weeks. In experiment 1, a two-bottle choice test (sucrose solution vs. water) was administered across five days to both nonhandled (NH) and maternally-separated (MS) offspring as adults and to dams 2-4 weeks post-weaning. In experiment 2, naltrexone was administered prior to two-bottle choice tests. MS males and the dams of MS litters exhibited increased intake of total fluid and sucrose solutions, whereas results from females were less consistent. Naltrexone elicited a greater decrease in fluid intake and sucrose intake in male MS offspring compared to male NH offspring. These results indicate that early postnatal stress alters both sucrose consumption, a non-drug measure of reward, and apparently the brain opioid systems that mediate naltrexone-induced drinking suppression.

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Periodic postpartum separation from the offspring results in long-lasting changes in anxiety-related behaviors and sensitivity to morphine in Long-Evans mother rats

Abstract: Multiple postpartum separations from the offspring alter the behavior of Long-Evans dams in novel/aversive environments and affect their sensitivity to the antinociceptive effects of morphine.

Cited by 43 publications

References 71 publications

Learning and memory deficits in mice lacking protease activated receptor-1

Learning and memory deficits in mice lacking protease activated receptor-1

Long-Lasting Changes in Morphine-Induced Locomotor Sensitization and Tolerance in Long-Evans Mother Rats as a Result of Periodic Postpartum Separation from the Litter: A Novel Model of Increased Vulnerability to Drug Abuse?

Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake and sucrose consumption in maternally separated rats

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