Ontogeny of cocaine-induced behaviors and cocaine pharmacokinetics in male and female neonatal, preweanling, and adult rats

McDougall, Sanders A.; Apodaca, Matthew G.; Mohd-Yusof, Alena; Mendez, Adrian D.; Katz, Caitlin G.; Teran, Angie; Garcia-Carachure, Israel; Quiroz, Anthony T.; Crawford, Cynthia A.

doi:10.1007/s00213-018-4894-8

Cited by 7 publications

(4 citation statements)

References 75 publications

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“…The present study extends those findings by: (a) testing multiple doses of reserpine (1 and 5 mg/kg), (b) assessing both male and female rats, (c) examining these drug effects during three ontogenetic periods (i.e., the preweanling period, adolescence, and adulthood), and (d) comparing the actions of ketamine to cocaine (10 and 15 mg/kg) and D -amphetamine (2 mg/ kg). These doses of cocaine and D -amphetamine were chosen because they produce substantial locomotor activity in all age groups tested [52][53][54][55]. In the companion paper to this study [56], the locomotor activating effects of ketamine, cocaine, and D -amphetamine were assessed in male and female rats pretreated with selective DA and 5-HT synthesis inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Effects of monoamine depletion on the ketamine-induced locomotor activity of preweanling, adolescent, and adult rats: Sex and age differences

Crawford

Moran

Baum

et al. 2020

Behavioural Brain Research

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Ketamine significantly increases the locomotor activity of rodents, however this effect varies according to the sex and age of the animal being tested. To determine the role monoamine systems play in ketamine's locomotor activating effects: (a) male and female preweanling, adolescent, and adult rats were pretreated with vehicle or the monoamine depleting agent reserpine (1 or 5 mg/kg), and (b) the behavioral actions of ketamine (20 or 40 mg/kg) were then compared to Damphetamine (2 mg/kg) and cocaine (10 or 15 mg/kg). The ability of reserpine to deplete dorsal striatal dopamine (DA) and serotonin (5-HT) in male and female rats was determined using HPLC. Ketamine caused substantial increases in the locomotion of preweanling rats and older female rats (adolescents and adults), but had only small stimulatory effects on adolescent and adult male rats. When compared to cocaine and D -amphetamine, ketamine was especially sensitive to the locomotor-inhibiting effects of monoamine depletion. Ketamine-induced locomotion is at least partially mediated by monoamine systems, since depleting DA and 5-HT levels by 87-96% significantly attenuated the locomotor activating effects of ketamine in male and female rats from all three age groups. When administered to reserpine-pretreated rats, ketamine produced a different pattern of behavioral effects than either psychostimulant, suggesting that ketamine does not stimulate locomotor activity via actions at the presynaptic terminal. Instead, our results are consistent with the hypothesis that ketamine increases locomotor activity through a down-stream mechanism, possibly involving ascending DA and/or 5-HT projection neurons.

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Section: Introductionmentioning

confidence: 99%

Effects of monoamine depletion on the ketamine-induced locomotor activity of preweanling, adolescent, and adult rats: Sex and age differences

Crawford

Moran

Baum

et al. 2020

Behavioural Brain Research

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“…Immediately after saline/ketamine injections, rats were placed in the testing chamber and locomotor activity, which was operationally defined as distance traveled (cm), was measured continuously across 12 ten-minute time blocks (2 h). Time blocks of this duration are sufficient to show time-dependent changes in the psychopharmacological effects of ketamine [25,26,43] and psychostimulant drugs [47][48][49].…”

Section: Experimental Designs and Proceduresmentioning

confidence: 99%

“…Moreover, there is equivocal evidence suggesting that PCPA may reduce the locomotor activating effects of MK-801 in male adult rats and mice [38]. As in our companion paper [43], male and female rats were also tested with doses of D-amphetamine (2 mg/kg) and cocaine (15 mg/kg) known to produce robust locomotor activity in rats of these ages [47][48][49]. These groups were included for comparison purposes, because there is evidence that ketamine may function like a psychostimulant at the presynaptic terminal [16,50,51; but see 52].…”

Section: Introductionmentioning

confidence: 99%

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

McDougall

Rios

Apodaca

et al. 2020

Behavioural Brain Research

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The pattern of ketamine-induced locomotor activity varies substantially across ontogeny and according to sex. Although ketamine is classified as an NMDA channel blocker, it appears to stimulate the locomotor activity of both male and female rats via a monoaminergic mechanism. To more precisely determine the neural mechanisms underlying ketamine's actions, male and female preweanling and adolescent rats were pretreated with vehicle, the dopamine (DA) synthesis inhibitor ∝-methyl-DL-p-tyrosine (AMPT), or the serotonin (5-HT) synthesis inhibitor 4-chloro-DLphenylalanine methyl ester hydrochloride (PCPA). After completion of the pretreatment regimen, the locomotor activating effects of saline, ketamine, D-amphetamine, and cocaine were assessed during a 2 h test session. In addition, the ability of AMPT and PCPA to reduce dorsal striatal DA and 5-HT content was measured in male and female preweanling, adolescent, and adult rats. Results showed that AMPT and PCPA reduced, but did not fully attenuate, the ketamine-induced locomotor activity of preweanling rats and female adolescent rats. Ketamine (20 and 40 mg/kg) caused a minimal amount of locomotor activity in male adolescent rats, and this effect was not significantly modified by AMPT or PCPA pretreatment. When compared to ketamine, Damphetamine and cocaine produced different patterns of locomotor activity across ontogeny; moreover, AMPT and PCPA pretreatment affected psychostimulant-and ketamine-induced locomotion differently. When these results are considered together, it appears that both dopaminergic and serotonergic mechanisms mediate the ketamine-induced locomotor activity of preweanling and female adolescent rats. The dichotomous actions of ketamine relative to the psychostimulants in vehicle-, AMPT-, and PCPA-treated rats, suggests that ketamine modulates DA and 5-HT neurotransmission through an indirect mechanism.

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“…Studies investigating sex differences in cocaine pharmacokinetics have yielded conflicting reports. Whereas many report no sex differences (Bowman et al, 1999; Mendelson et al, 1999; Evans and Foltin, 2010; Coe et al, 2018, McDougall et al, 2018) others find the metabolism of cocaine varies with sex (Niyomachi et al, 2066; Visalli et al, 2005). It must be emphasized that pharmacokinetics studies are complex, and multiple factors, such as age, dose, individual differences in metabolism among others can affect the results obtained.…”

Section: Introductionmentioning

confidence: 99%

Cocaine sensitization in male rats requires activation of estrogen receptors

Menéndez-Delmestre,

Agosto-Rivera,

González-Segarra

et al. 2024

Preprint

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Gonadal steroids play a modulatory role in cocaine use disorders, and are responsible for many sex differences observed in the behavioral response to cocaine. In females, it is well established that estradiol enhances the behavioral response to cocaine. In males, we have recently shown that testosterone enhances sensitization to cocaine but its mechanism of action remains to be elucidated. The current study investigated the contribution of DHT, a non-aromatizable androgen, and of estradiol, in regulating cocaine-induced sensitization in male rats. Gonadectomized (GDX) male rats treated with estradiol sensitized to repeated cocaine administration, while GDX rats treated with DHT did not, implicating estradiol in cocaine sensitization. Furthermore, intact male rats treated with the antiestrogen ICI 182,780 did not show sensitization to repeated cocaine. This study demonstrates the pivotal role of estradiol in cocaine-induced neuroplasticity and neuroadaptations in the rodent brain.

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Ontogeny of cocaine-induced behaviors and cocaine pharmacokinetics in male and female neonatal, preweanling, and adult rats

Cited by 7 publications

References 75 publications

Effects of monoamine depletion on the ketamine-induced locomotor activity of preweanling, adolescent, and adult rats: Sex and age differences

Effects of monoamine depletion on the ketamine-induced locomotor activity of preweanling, adolescent, and adult rats: Sex and age differences

Effects of dopamine and serotonin synthesis inhibitors on the ketamine-, d-amphetamine-, and cocaine-induced locomotor activity of preweanling and adolescent rats: sex differences

Cocaine sensitization in male rats requires activation of estrogen receptors

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