Altered behavioral responsivity to morphine during the periadolescent period in rats

Spear, Linda P.; Horowitz, Gary P.; Lipovsky, Julie A.

doi:10.1016/0166-4328(82)90005-5

Cited by 45 publications

(30 citation statements)

References 23 publications

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“…Our data confirm the findings of previous preclinical studies demonstrating both age-and sexrelated behavioral differences in motor activity between periadolescent and adult rats under basal conditions and in response to morphine (Spear et al, 1982;White and Holtzman, 2005). The principal new contributions of this study were to extend those observations to include a) age-related differences in response to the acute antinociceptive effects of morphine, and b) the impact of varying levels of morphine exposure during periadolescence (versus adulthood) on sensitivity to morphine-induced motor activity later in life in both male and female rats.…”

Section: Discussionsupporting

confidence: 81%

“…Additionally, previous work from our laboratory demonstrated that periadolescent rats treated with morphine (10 mg/kg/day) for three days were more responsive to morphine-induced locomotion compared to saline-treated cohorts when tested as young adults-an effect not shared by their adult-treated counterparts (White and Holtzman, 2005). In light of these findings, the purpose of the current study was extend our previous observations (White and Holtzman, 2005) as well as those of others (Spear et al, 1982), using well-validated assays of effects of morphine. First, we determined the effects of age on acutely administered morphine-induced antinociception.…”

supporting

confidence: 45%

“…In one study, acutely administered morphine (1.0-10 mg/kg) induced greater locomotor responses in male and female periadolescent rats compared with adult rats (Spear et al, 1982). Additionally, previous work from our laboratory demonstrated that periadolescent rats treated with morphine (10 mg/kg/day) for three days were more responsive to morphine-induced locomotion compared to saline-treated cohorts when tested as young adults-an effect not shared by their adult-treated counterparts (White and Holtzman, 2005).…”

mentioning

confidence: 99%

“…Additionally, a number of gender differences have been reported in several aspects of opioid pharmacology, including antinociceptive (Cicero et al, 1996;Bartok and Craft, 1997) effects as well as drug-induced locomotion (Spear et al, 1982) and discriminative-stimulus (Craft et al, 1996) effects. Based on these studies, and our previous findings suggesting that periadolescent rats are more sensitive to the long-term effects of morphine, we hypothesized that periadolescent male and female rats would show greater morphine-induced antinociception and locomotor activity compared to their adult counterparts.…”

mentioning

confidence: 99%

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Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats

White

Michaels

Holtzman

2008

Pharmacology Biochemistry and Behavior

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Little has been done to investigate the effects of opioid exposure during adolescence. Therefore, our first objective was to determine behavioral differences in response to acutely administered morphine (e.g., antinociception and locomotion) between periadolescent and adult male and female rats. Our second objective was to determine the impact of age of morphine exposure on sensitivity to morphineinduced locomotion later in life. For the acute morphine studies, antinociceptive responses (using tail-flick and hot plate latencies) were assessed using cumulative morphine dosing (0.5-12 mg/kg) followed by a time course after the last morphine injection (up to 4 hr), and dose-response curves for motor activity (2 h test) were determined following saline and morphine (0.1-3.0 mg/kg) administration. For the long-term study, periadolescent and adult rats were given one of four treatment regimens (saline or one, three, or five days of morphine; 5.0 mg/kg, 2X/day). Changes in locomotor activity in response to saline or morphine (0.1-3.0 mg/kg) were determined one month later. A number of age-and sex-related behavioral differences were observed: basal differences in behavior were assay-dependent; however, male periadolescent rats were generally more sensitive to acute morphine-induced motor stimulation, while both male and female periadolescent rats tended to be less sensitive to morphine-induced antinociception. Lastly, following morphine exposure, activity was dependent on age of treatment and treatment regimen, with the greatest effects in fiveday periadolescent-treated animals. These findings demonstrate that the sensitivity of periadolescent rats to the acute and protracted effects of morphine is different from that of adult rats.

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Section: Discussionsupporting

confidence: 81%

supporting

confidence: 45%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats

White

Michaels

Holtzman

2008

Pharmacology Biochemistry and Behavior

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“…The adolescent rodent is considered a valid model for developmental changes in vulnerability to drugs of abuse (Spear and Brake, 1983;Laviola et al, 1999). For example, sensitivity to morphine-induced locomotion is more evident in adolescent compared to adult rats (Spear et al, 1982) and novelty seeking and amphetamine sensitization are greater in adolescents (Adriani and Laviola, 2004). On the other hand, morphine and cocaine-induced conditioned place preference do not appear to differ in adolescent and adult rats (Campbell et al, 2000) indicating that not all drugrelated behaviors are enhanced during adolescence.…”

Section: Introductionmentioning

confidence: 99%

Behavioral and Electrophysiological Evidence for Opioid Tolerance in Adolescent Rats

Ingram

Fossum

Morgan

2006

Neuropsychopharmacol

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Morphine and other opiates are successful treatments for pain, but their usefulness is limited by the development of tolerance. Given that recent studies have observed differential sensitivity to drugs of abuse in adolescents, the aim of this study was to assess antinociceptive tolerance to morphine in adolescent rats using both behavioral and cellular measures. Early (28-35 days postnatal) and late (50-59 days) adolescent and adult (73-75 days) male rats were injected with morphine (5 mg/kg, s.c.) or saline twice a day for two consecutive days. On Day 3, tolerance to morphine was evident in morphine-pretreated rats when tested on the hot plate test. Although baseline latencies for the early compared to late adolescent rats were faster, the magnitude of the shift in ED 50 for morphine was similar for the two adolescent groups. However, the shift in ED 50 tended to be greater in adolescent compared to adult rats. Subsequent to behavioral testing, whole cell patch-clamp recordings were made from ventrolateral PAG neurons. The opioid agonist, met-enkephalin (ME), activated similar outward currents in PAG neurons of early and late adolescent rats. However, reversal potentials of ME-induced currents were shifted to more hyperpolarized potentials in cells from morphine-pretreated rats. In addition, ME induced larger currents in morphine-pretreated rats with faster hot plate latencies compared to the mean (more tolerant) than in rats with slower latencies. These results indicate that repeated intermittent administration of morphine produces tolerance in adolescent rats that is associated with novel changes in opioid-sensitive ventrolateral PAG neurons.

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Periadolescence: Age‐dependent behavior and psychopharmacological responsivity in rats

Spear

Brake

1983

Developmental Psychobiology

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502

333

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The behavior and psychopharmacological sensitivity of periadolescent rats are examined in this review. Periadolescent rats are hyperactive and engage in more conspecific play behavior than younger or older rats. When compared with other-aged rats, periadolescents exhibit enhanced performance in simple active-avoidance learning tasks, but perform poorly in more complex appetitive and avoidance learning tasks in which increases in locomotor activity do not improve performance, perhaps as a result of age-specific alterations in selective attention or stimulus processing. Such behavioral "anomalies" of periadolescent animals observed in traditional laboratory situations may be in some way adaptive when considered in the context of the animals' natural habitat. In terms of psychopharmacological responsiveness, periadolescent rats, when compared with younger or older animals, are less sensitive to catecholaminergic agonists but are more responsive to the catecholaminergic antagonist haloperidol. This pattern of psychopharmacological sensitivity suggests that the catecholaminergic systems may be temporarily hyposensitive during the periadolescent period. Evidence is presented that a negative feedback system in the form of dopamine autoreceptors may become functionally mature in mesolimbic brain regions during the periadolescent period. The possibility is presented that maturation of these self-inhibitory autoreceptors might result in a temporary decrease in the efficacy of mesolimbic dopamine projections, perhaps contributing to the psychopharmacological and behavioral characteristics of periadolescent animals. In support of this suggestion, evidence is reviewed indicating that the behavior of adult animals with lesions of the ventral tegmental area, a region containing cell bodies from which these mesolimbic dopaminergic projections originate, resembles that of periadolescent rats.

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Altered behavioral responsivity to morphine during the periadolescent period in rats

Cited by 45 publications

References 23 publications

Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats

Periadolescent male but not female rats have higher motor activity in response to morphine than do adult rats

Behavioral and Electrophysiological Evidence for Opioid Tolerance in Adolescent Rats

Periadolescence: Age‐dependent behavior and psychopharmacological responsivity in rats

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