Amphetamine Treatment During the Preweanling Period Produces Enduring Changes in Striatal Protein Kinase A Activity

Crawford, Cynthia A.; Zavala, Arturo R.; Karper, Patrick E.; Collins, Robert L.; Loring-Meier, Torran; Watson, Joseph B.; McDougall, Sanders A.

doi:10.1016/s0091-3057(00)00289-6

Cited by 9 publications

(8 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability of MDMA to induce long-term declines in PKA activity has not been previously reported; however, this result is consistent with studies showing that PKA activity is reduced after early exposure to amphetamine or methamphetamine (Crawford et al, 2000a(Crawford et al, ,b, 2003. We previously hypothesized that psychostimulant-induced decreases in dorsal striatal PKA activity were due to either a down-regulation of DA D 1 receptors (which are coupled to G s G proteins) or an up-regulation of DA D 2 receptors (which are coupled to G i G proteins).…”

Section: Discussionsupporting

confidence: 89%

“…Instead, early exposure to MDMA may affect learning and memory processes by causing long-term alterations in cyclic adenosine monophosphate (cAMP) signal transduction mechanisms. This hypothesis is supported by two sets of findings: (i) early exposure to other amphetamine analogs (D-amphetamine and Dmethamphetamine) causes long-term declines in dorsal striatal and accumbal cAMP-dependent protein kinase A (PKA) activity (Crawford et al, 2000a(Crawford et al, ,b, 2003; and (ii) decreased PKA activity is associated with hippocampal memory impairment (Abel et al, 1997;Nagakura et al, 2002;Wu et al, 2002). MDMA-induced changes in PKA activity are most likely due to altered receptor/G protein coupling because many monoamine receptors are coupled to the cAMP transduction system.…”

Section: Introductionmentioning

confidence: 92%

See 1 more Smart Citation

Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats

et al. 2006

View full text Add to dashboard Cite

Recreational use of methylenedioxymethamphetamine (MDMA) has dramatically increased among juveniles and young adults of child-bearing age, and the potential for fetal exposure has increased. For this reason, it is surprising that comparatively few studies have assessed the long-term impact of early MDMA exposure on serotonin (5-HT) and dopamine (DA) neurotransmitter systems. The purpose of this study was to determine whether repeated exposure to MDMA during the preweanling period would cause long-term changes in 5-HT and DA functioning. Rats were treated with saline or 20 mg/kg MDMA (two injections per day) from postnatal day (PD) 11-20. At PD 90, rats were killed, and their dorsal striatum, prefrontal cortex, and hippocampus were removed. 5-HT and DA content, as well as their metabolites, were measured using HPLC. In addition, cAMP-dependent protein kinase A (PKA) activity and agonist-stimulated [ 35 S]GTPγS binding was assayed using tissue homogenates from each brain region. Results indicated that early MDMA exposure caused a decrease in PKA activity and 5-HT content in the prefrontal cortex and hippocampus while increasing the efficacy of 5-HT 1A receptors as measured by agonist-stimulated [ 35 S]GTPγS binding. Additionally, DA content was reduced in the dorsal striatum and prefrontal cortex. These data indicate that early MDMA exposure has long-term effects on the 5-HT and DA neurotransmitter systems that may be mediated, at least partially, by changes in 5-HT 1A receptor sensitivity.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 92%

Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats

et al. 2006

View full text Add to dashboard Cite

show abstract

“…While the present results are the first direct demonstration that PKA signaling modulates the stimulant effects of ethanol and ethanol-induced behavioral sensitization, previous pharmacological and genetic studies have established that PKA signaling is involved with amphetamine- (Crawford et al, 2004;Crawford et al, 2000;Tolliver et al, 1999) and cocaine- (Miserendino and Nestler, 1995;Park et al, 2000;Schroeder et al, 2004) induced locomotor sensitization. Of direct relevance to the present report is the observation that RIIβ −/− mice are more susceptible to the acquisition of locomotor sensitization following repeated amphetamine exposure (Brandon et al, 1998).…”

Section: Discussionsupporting

confidence: 44%

Involvement of protein kinase A in ethanol-induced locomotor activity and sensitization

et al. 2006

View full text Add to dashboard Cite

These data provide novel evidence implicating an influence of protein kinase A signaling on ethanol-induced locomotor activity and behavioral sensitization. The observation that RIIbeta(-/-) mice are more sensitive to the effects of repeated ethanol administration suggests that normal protein kinase A signaling limits, or is protective against, the stimulant effects of ethanol and the plastic alterations that underlie behavioral sensitization.

show abstract

“…They have full use of all major senses, a remarkable adult-like capacity for locomotor activity, and high levels of response to specific stimuli in their environment [58,59]. This is a period just before weaning (days [18][19][20][21][22], when they still require some nursing and protection by their mother but are first allowed out of an otherwise mother-controlled nest area [5,26,27,45,54].…”

Section: Introductionmentioning

confidence: 99%

“…injections [18,40,72,82,83]. 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].…”

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

View full text Add to dashboard Cite

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.

show abstract

Amphetamine Treatment During the Preweanling Period Produces Enduring Changes in Striatal Protein Kinase A Activity

Cited by 9 publications

References 39 publications

Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats

Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPγS binding in adult rats

Involvement of protein kinase A in ethanol-induced locomotor activity and sensitization

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

Contact Info

Product

Resources

About