Ontogeny of dopamine agonist-induced sensitization: role of NMDA receptors

Duke, Marcus; O'Neal, J. Laurel; McDougall, Sanders A.

doi:10.1007/s002130050175

Cited by 33 publications

(33 citation statements)

References 36 publications

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“…Most studies on behavioral sensitization to psychostimulants are performed on adult rats, although there are reports that demonstrate young rats also show sensitized behavioral responses to amphetamine (McDougall et al, 1994;Duke et al, 1997). Prior to initiating physiological investigations of glutamatergic synapses, we wanted to confirm that the young rats used in our physiological experiments exhibit a sensitized response to amphetamine.…”

Section: Resultsmentioning

confidence: 99%

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and it has been hypothesized that drug exposure triggers synaptic plasticity of glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area. Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR ratio. We tested the prediction that an increase in GluR1-containing AMPA receptors would result in an increase in GluR1 homomeric receptors at synapses, but were unable to observe any evidence of the predicted rectification in DA neurons from animals treated with amphetamine. We also examined the possibility of increased AMPA receptor insertion in the membrane, but did not detect a significant increase in biotinylated surface GluR1. We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse.

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Section: Resultsmentioning

confidence: 99%

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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“…Various factors might be responsible for this ontogenetic difference in behavioral sensitization, including drug pharmacokinetics, age-dependent differences in dopamine and glutamate neuronal systems, and changes in associative learning abilities. Although an obvious possibility, there is little evidence suggesting that ontogenetic changes in dopaminergic and glutamatergic systems are responsible for age-dependent differences in behavioral sensitization (Duke et al 1997). For example, by 15 days of age, striatal dopamine (D 1 -like and D 2 -like) and glutamate [N-methyl-D-aspartate (NMDA) and non-NMDA] receptor levels have reached adult values (Gelbard et al 1989;Insel et al 1990;Miller et al 1990;Rao et al 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, young rats do not appear to show adult-like behavioral sensitization. More specifically, young rats will exhibit a sensitized response after one or two abstinence days (McDougall et al 1994;Bowman et al 1997;Duke et al 1997;Tirelli and Ferrara 1997;Wood et al 1998); however, behavioral sensitization is typically not observed after a more extended abstinence period (Fujiwara et al 1987;Kolta et al 1990;McDougall et al 1994;Ujike et al 1995). Two exceptions to this pattern of results have been reported, as young rats given repeated injections of a high dose of methylphenidate (20 mg/kg) exhibited long-term maintenance of a sensitized sniffing response (McDougall et al 1999).…”

Section: Introductionmentioning

confidence: 89%

Cocaine-induced behavioral sensitization in the young rat

Zavala¹,

Nazarian²,

Crawford³

et al. 2000

Psychopharmacology

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Rationale: Repeated psychostimulant treatment has been shown to sensitize the locomotor activity of young rats, but there is conflicting evidence suggesting that this sensitized response will persist across only a few drug abstinence days. Objective: The purpose of the present study was to determine whether: (a) young rats are capable of expressing a sensitized locomotor response after an extended drug abstinence period, and (b) the longevity of the sensitized response is critically affected by either the number of drug pretreatment days or environmental conditioning factors. Methods: Young rats were pretreated with saline or cocaine (15 mg/kg or 30 mg/kg, i.p.) for either five or ten consecutive days [i.e., on postnatal days (PD) 16-20 or PD 11-20]. After each daily injection, rats were placed in activity chambers, and locomotion was measured for 30 min. To assess environmental conditioning factors, some rats were injected with saline prior to being placed in the activity chambers and then injected with cocaine prior to being returned to the home cage. After one or seven abstinence days (i.e., on PD 22 or PD 28), rats received a challenge injection of saline or cocaine (15 mg/kg) in the activity chamber and locomotion was assessed. Results: Young rats exhibit cocaine-induced locomotor sensitization after either a short (1-day) or long (7-day) drug abstinence period. When a long abstinence period was used, locomotor sensitization was only apparent when cocaine pretreatment lasted for 10 days. Conditioning factors were also important for determining whether locomotor sensitization was expressed, because young rats pretreated with cocaine in the home cage did not show a sensitized locomotor response after seven abstinence days. Conclusions: Young rats are capable of showing cocaine-induced locomotor sensitization after an extended abstinence period. Both the number of drug pretreatment days and the environmental context in which cocaine was given (i.e., the activity chamber or home cage) influenced the longevity of cocaine-induced locomotor sensitization.

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“…It has been reported that moderate doses of MK801 (but not higher doses) prevent D1 dopamine receptor supersensitivity [45] and dopamine release [1] . Furthermore, behavioral sensitization induced by dopaminergic agonists may be prevented by moderate doses of MK801 [46] . Interestingly, the dopaminergic system also regulates NMDA receptor function.…”

Section: Discussionmentioning

confidence: 99%

Morphine-Induced Behavioral Sensitization Increased the mRNA Expression of NMDA Receptor Subunits in the Rat Amygdala

et al. 2008

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This study was designed to evaluate the effect of repeated morphine treatment on rat behavioral responses. In the genetic section, the mRNA expression of NMDA receptor subunits (NR1 and NR2A) was measured in certain areas of the male rat brain (striatum, prefrontal cortex, hippocampus, hypothalamus and amygdala). In the behavioral section, the effect of repeated morphine treatment on animal models such as locomotion, oral stereotypy, and state-dependent memory in a passive avoidance test was evaluated in the presence or absence of MK801 (NMDA receptor antagonist). Our results showed that chronic morphine treatment, followed by a 7-day (but not 24-hour) washout period, potentiated the effect of test doses of morphine, which is referred to as behavioral sensitization. Meanwhile, pretreatment of animals with MK801 (0.1 and 0.25 mg/kg), 30 min before a test dose of morphine (5 mg/kg), failed to attenuate the locomotion and oral stereotypy in the behavioral sensitization state. Interestingly, a higher dose of MK801 (0.25 mg/kg) decreased memory retrieval induced by morphine (2.5 mg/kg) in state-dependent memory. This effect may be due to the intrinsic motor enhancer property of higher doses of MK801, rather than the blockade of NMDA receptors. It can be concluded that MK801 does not affect morphine-induced behavioral sensitization in the expression phase. In the genetic section of the study, results of quantitative real-time RT-PCR clearly indicated that morphine sensitization increased the expression of NMDA receptor subunits mRNA in the amygdala (NR1 by 104% and NR2A by 85%), while the other areas of the brain were unaffected. Maenwhile, no change in the mRNA levels was observed in non-sensitized animals (chronic morphine treatment followed by a 24-hour washout period). In summary, the present study indicates that repeated morphine treatment followed by long-term (7-day washout) induces behavioral sensitization and causes a delayed increase in mRNA levels of NMDA receptor subunits in the rat amygdala. Meanwhile, it has previously been reported that the amygdala is involved in behavioral sensitization. Thus, it can be concluded that the increase in NMDA receptor expression is associated with morphine-induced behavioral sensitization.

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Ontogeny of dopamine agonist-induced sensitization: role of NMDA receptors

Cited by 33 publications

References 36 publications

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Cocaine-induced behavioral sensitization in the young rat

Morphine-Induced Behavioral Sensitization Increased the mRNA Expression of NMDA Receptor Subunits in the Rat Amygdala

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