Cocaine differentially alters behavior and neurochemistry in periadolescent versus adult rats

Collins, Stephanie L.; Izenwasser, Sari

doi:10.1016/s0165-3806(02)00471-6

Cited by 86 publications

(85 citation statements)

References 35 publications

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“…On the other hand, in the study by (Spear and colleagues 1982), drug doses were expressed as the salt form, whereas drug doses in the current study were expressed in terms of the base, potentially reducing differences between the two studies. Regardless, the overall findings of this study and those of (Spear and colleagues 1982) are in line with those of other studies of age-related (Spear and Brake, 1983;Collins and Izenwasser, 2002;Vastola et al, 2002;Schochet et al, 2004) and age-and sex-related (Collins and Izenwasser, 2004) differences in motor response to drugs of abuse.…”

Section: Discussionsupporting

confidence: 92%

“…These ontogenic differences also result in differential sensitivity to the locomotor stimulatory effect of drugs of abuse, including cocaine (Laviola et al, 1995;Collins and Izenwasser, 2002), methylphenidate (Brandon et al, 2001), and nicotine (Faraday et al, 2001;Schochet et al, 2004). These age-related differences extend to other drug-induced behavioral effects as well.…”

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: 92%

mentioning

confidence: 99%

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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“…In contrast, during the first two exposures, preweanling rats showed an increased locomotor response (like sensitization) over the entire three hour test period but by the third exposure activity over the three hours was decreasing compared to prior days (tolerance-like response). This was similar to findings in periadolescent rats showing no increased locomotor response in the sequence of 7 daily exposures (a higher dose than we used), and no evidence of sensitized response with challenge after drug vacation [17]. Together, these data [17] and our data suggest that drug-induced locomotor responses in the young have a pattern that differs from the adult when both the rising and falling phases of the plasma levels are considered.…”

Section: Discussionsupporting

confidence: 90%

“…This was similar to findings in periadolescent rats showing no increased locomotor response in the sequence of 7 daily exposures (a higher dose than we used), and no evidence of sensitized response with challenge after drug vacation [17]. Together, these data [17] and our data suggest that drug-induced locomotor responses in the young have a pattern that differs from the adult when both the rising and falling phases of the plasma levels are considered.…”

Section: Discussionsupporting

confidence: 90%

Behavioral responses during the initial exposures to a low dose of cocaine in late preweanling and adult rats

Smith

Morrell

2008

Neurotoxicology and Teratology

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Human drug experimentation begins during late childhood and early adolescence, a critical time in physical and CNS development, when the immature CNS is vulnerable to the long-term effects of psychoactive drugs. Few preclinical animal studies have investigated responses to such drugs in a developmental stage equivalent to late childhood of humans. We used a rodent model to examine behavioral responses of female Sprague-Dawley late preweanling and adult rats during acute and repeated exposures to a low dose of cocaine. Results show that after cocaine injection, preweanling rats (18-21 days old) have locomotor responses that differ from adults, but after postnatal day 22, the responses are indistinguishable from adults even though rats are still not weaned. Before day 22, locomotor effects of cocaine differ from those in adults in three ways: preweanlings are active for a longer time after cocaine injection at day 18; preweanling activity peaks more rapidly after subcutaneous administration; and after only three injections of cocaine, a tolerance-like pattern is seen in preweanlings whereas an emerging pattern of sensitization to cocaine is seen in adults. The behavioral patterns of this age group offer a preclinical model of the early effects of drugs of abuse.

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“…Responses to psychostimulants vary with age such that during adolescence and adulthood stimulants elicit euphoric responses, whereas they have been described as dysphoric by children (Rapoport et al, 1980). Most preclinical studies also indicate that the effects of stimulants increases with age (Cirulli and Laviola, 2000;Collins and Izenwasser, 2002;Tirelli et al, 2003). One model used to ascertain the rewarding properties of drugs in rodents is conditioned place preference (Bardo and Bevins, 2000).…”

Section: Introductionmentioning

confidence: 99%

Trk: A Neuromodulator of Age-Specific Behavioral and Neurochemical Responses to Cocaine in Mice

Niculescu¹,

Perrine²,

Miller³

et al. 2008

J. Neurosci.

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Responses to psychostimulants vary with age, but the molecular etiologies of these differences are largely unknown. The goal of the present research was to identify age-specific behavioral and molecular adaptations to cocaine and to elucidate the mechanisms involved therein. Postweanling, periadolescent, and adult male CD-1 mice were exposed to cocaine (20 mg/kg) for 7 d. The rewarding effects of cocaine were assessed, as were the response to a Trk antagonist and the regulation of dopamine and cAMP-regulated phosphoprotein, 32 kDa (DARPP-32). Cocaine was rewarding in both periadolescent and adult mice using a conditioned place preference procedure. In contrast, postweanling mice failed to demonstrate significant cocaine-induced place preference. Because components of the neurotrophin system including brain-derived neurotrophic factor and TrkB are developmentally regulated, their role in the age-specific effects of cocaine was determined using the Trk receptor antagonist K252a. Postweanling mice that received K252a before daily cocaine showed a significant place preference to the cocaine-paired environment that was not seen in the absence of K252a. DARPP-32 protein levels were significantly upregulated in the lateral region of the caudate-putamen exclusively in postweanling mice after chronic cocaine. Daily pretreatment with K252a attenuated the induction of DARPP-32 in the postweanling striatum. These data indicate that Trk neurotransmission plays a role in age-specific behavioral and molecular responses to cocaine and concurrently modulates DARPP-32 levels.

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Cocaine differentially alters behavior and neurochemistry in periadolescent versus adult rats

Cited by 86 publications

References 35 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 responses during the initial exposures to a low dose of cocaine in late preweanling and adult rats

Trk: A Neuromodulator of Age-Specific Behavioral and Neurochemical Responses to Cocaine in Mice

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