Cocaine-induced behavior in the developing rat

Spear, Linda P.; Brick, John

doi:10.1016/s0163-1047(79)91410-9

Cited by 90 publications

(69 citation statements)

References 16 publications

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“…The mean age and range on the day of the experiment was 28 (27)(28)(29)(30) and 68 (60)(61)(62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77) for the PN28 and PN65 groups, respectively. Varying the frequency of electrical stimulation evokes steady-state responses at low frequencies (20 Hz) as uptake and release are balanced, and linear increases at high frequencies (60 Hz) as release overwhelms uptake.…”

Section: Resultsmentioning

confidence: 99%

“…Several groups have reported that animals in the periadolescent period, , are in general hyperactive, but have smaller increases in locomotion and stereotypic behaviors than younger or older cohorts after single treatments with amphetamine [8,34,70] or cocaine [8,41,63]. Others have reported that adolescents are more responsive to cocaine [11,12,35], amphetamine [1] or nicotine [4,16].…”

Section: Introductionmentioning

confidence: 99%

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Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Walker

Kuhn

2008

Neurotoxicology and Teratology

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The neural mechanisms responsible for the enhanced adolescent vulnerability for initiating drug abuse are unclear. We investigated whether age differences in dopamine neurotransmission could explain cocaine's enhanced psychomotor effects in the periadolescent rat. Electrical stimulation the medial forebrain bundle of anesthetized post-natal age 28 days (PN28) and PN65 rats elicited dopamine release in caudate nucleus and nucleus accumbens core before and after 15 mg/kg cocaine i.p. Extracellular dopamine concentrations were greater in PN65 than PN28 caudate following 20 and 60Hz stimulations and in the PN65 nucleus accumbens following 60Hz stimulations. Cocaine increased dopamine concentrations elicited by 20 Hz stimulations 3-fold in the adult, but almost 9-fold in periadolescent caudate. Dopamine release rate was lower in the periadolescent caudate although total dopamine clearance was similar to that of adults. The periadolescent caudate achieved adult levels of clearance by compensating for a lower V max with higher uptake affinity. Tighter regulation of extracellular dopamine by the higher uptake/release ratio in periadolescents led to greater increases after cocaine. In nucleus accumbens, dopamine release and V max were lower in periadolescents than adults, but uptake affinity and cocaine effects were similar. Immaturity of dopamine neurotransmission in dorsal striatum may underlie enhanced acute responses to psychostimulants in adolescent rats and suggests a mechanism for the greater vulnerability of adolescent humans to drug addiction.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Walker

Kuhn

2008

Neurotoxicology and Teratology

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“…Others have also examined the impact of pharmacologic interventions during infancy and adolescence (Dahl & Spear, 2004;Spear, 2000;Spear & Brick, 1979). It is likely that susceptibility to long-term changes in this period is facilitated by the notable physiological and neural sculpting also known to be a feature of this stage (for a review, see Spear, 2000).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Comparison of infant and adult rats in exploratory activity, diurnal patterns, and responses to novel and anxiety-provoking environments.

Smith¹,

Morrell²

2007

Behavioral Neuroscience

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Infant rats emerge from the maternal nest at Postnatal Day 17-18 to have their first critical environmental experiences; they may be particularly sensitive to experiences or experimental interventions that can affect their adult capacity. The authors address open questions on 2 components of normative environmental exploration, locomotor activity and response to anxiety-provoking locations, in Postnatal Day 18 infant and Postnatal Day 60 adult rats. The authors compare diurnal patterns of locomotor activity, wheel running, novel and familiar open-field activity, and 2 measures of anxiety. Infants have an equivalent capacity to adults for locomotor activity and wheel running and a fundamentally adult-like diurnal rhythm, except that they do not anticipate light-dark transitions, are more perturbable at their most somnolent, and are more or less active during specific limited phases than adults. Infants initially have a lower rate of locomotor activity in novel environments and have a greater willingness to be active in anxiety-provoking locations. Such differences may allow enhanced gathering of environmental information by the infant and are important to consider in the design of experiments using infants. Keywordsinfant; adult; exploration; activity; anxiety In humans, late childhood and adolescence is the period when drug sampling and experimentation first begins (Brown & Tapert 2004;Johnston, O'Malley, Bachman, & Schulenberg, 2005;Spear, 2000;Turner, Mermelstein, & Flay, 2004), when clinical mental health disorders requiring pharmacologic intervention, such as attention-deficit/hyperactivity disorder, emerge (Andersen, 2003;Andersen, Arvanitogiannis, Pliakas, LeBlanc, & Carlezon, 2002), and when the central nervous system (CNS) is readily shaped by many stimuli, often with long-lasting consequences. Ultimately, studies using immature animals may inform us about human disorders with early life origins (e.g., hyperactivity) and may inform the beneficial use of pharmacological treatments. Further, these studies may provide insight into the effects of preadolescent sampling of drugs of abuse (Dahl & Spear, 2004).Prior to achieving sexual maturity between Postnatal Days (P) 55-60, immature rats are either infants (P1-P28) or adolescents (P28-P55; Ojeda & Urbanski, 1988;Spear, 2000). Infant rats are vigilantly kept in the protective maternal nest by their mothers until around P17-P18 (Barnett, 1958;Galef & Clark, 1972; Pereira & Morrell, 2007;Small, 1899), when they are allowed out into their larger environment. At this point, they have full motor and sensory capacity (Moorcroft, Lyttle, & Campbell, 1971). Experiences at this point readily produce longCorrespondence concerning this article should be addressed to Kiersten S. Smith, Center for Molecular and Behavioral Neuroscience, Rutgers University, 197 University Avenue, Newark, NJ 07102. E-mail: kismith@pegasus.rutgers.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript term effects; enriched environments lead...

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“…In additional studies, multiple doses of stimulants were administered to preweanling or adolescent animals, but those studies examined the effects of the long-term expression of sensitization either later in adolescence [58,68,72] or in adulthood [72]. To date, only one study has examined infant, late preweanling and adolescent responses to s.c. injections of cocaine [62] and characterized the immediate effects of the drug. All of those studies documented locomotor behavior during the first 30-60 min after cocaine injection, which is the rising phase of the blood levels of cocaine.…”

Section: Introductionmentioning

confidence: 99%

“…This work is part of our series of studies of the effects of cocaine on female rats of various endocrine states [43,74,77]. Although there are gender differences in cocaine response in adults [23,42], none are found in preweanling rats [62]. We examined behavioral responses during the first few exposures to cocaine because our working hypothesis is that such a preclinical model using low doses in this manner mimics the pattern of initial sampling of drugs of abuse by young humans prior to the onset of bingeing behavior [7,14,19].…”

Section: Introductionmentioning

confidence: 99%

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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Cocaine-induced behavior in the developing rat

Cited by 90 publications

References 16 publications

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Cocaine increases stimulated dopamine release more in periadolescent than adult rats

Comparison of infant and adult rats in exploratory activity, diurnal patterns, and responses to novel and anxiety-provoking environments.

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

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