The role of D1 and D2 dopamine receptors in the acquisition and expression of cocaine-induced conditioned increases in locomotor behavior

Fontana, David; Rm, Post; Weiss, Stéphanie; Pert, Agu

doi:10.1097/00008877-199308000-00011

Cited by 53 publications

(70 citation statements)

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“…Repeated local injections of the D 1 /D 5 receptor agonist SKF38393 into the VTA also produce behavioral sensitization to systemic cocaine (Pierce et al, 1996). Previous studies have shown that the D 1 /D 5 receptor antagonist SCH23390 blocks context-dependent or one-shot sensitization (Fontana et al, 1993) and the development of sensitization to cocaine as measured at 3 d of withdrawal (White et al, 1998). These studies suggest that sensitization to cocaine may involve DA D 5 receptors in the VTA.…”

Section: Discussionmentioning

confidence: 99%

Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D₅Receptor-Dependent Redistribution of NMDA Receptors

et al. 2006

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Cocaine-induced plasticity of glutamatergic synaptic transmission in the ventral tegmental area (VTA) plays an important role in brain adaptations that promote addictive behaviors. However, the mechanisms responsible for triggering these synaptic changes are unknown. Here, we examined the effects of acute cocaine application on glutamatergic synaptic transmission in rat midbrain slices. Cocaine caused a delayed increase in NMDA receptor (NMDAR)-mediated synaptic currents in putative VTA dopamine (DA) cells. This effect was mimicked by a specific DA reuptake inhibitor and by a DA D 1 /D 5 receptor agonist. The effect of cocaine was blocked by a DA D 1 /D 5 receptor antagonist as well as by inhibitors of the cAMP/cAMP-dependent protein kinase A (PKA) pathway. Furthermore, biochemical analysis showed an increase in the immunoreactivity of the NMDAR subunits NR1 and NR2B and their redistribution to the synaptic membranes in VTA neurons. Accordingly, NMDAR-mediated EPSC decay time kinetics were significantly slower after cocaine, suggesting an increased number of NR2B-containing NMDARs. Finally, pharmacological analysis indicates that NR2B subunits might be incorporated in triheteromeric NR1/NR2A/NR2B complexes rather than in "pure" NR1/NR2B NMDA receptors. Together, our data suggest that acute cocaine increases NMDAR function in the VTA via activation of the cAMP/PKA pathway mediated by a DA D 5 -like receptor, leading to the insertion of NR2B-containing NMDARs in the membrane. These results provide a potential mechanism by which acute cocaine promotes synaptic plasticity of VTA neurons, which could ultimately lead to the development of addictive behaviors.

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Section: Discussionmentioning

confidence: 99%

Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D₅Receptor-Dependent Redistribution of NMDA Receptors

et al. 2006

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“…The increase in locomotor sensitivity to cocaine and quinpirole as well as the enhanced development of cocaine CPP may be mediated by the increases in dopamine D 2 receptor expression observed in the NAc. Previous work has shown that dopamine D 2 receptors are necessary for the development of cocaine sensitization (Fontana et al, 1993), and that increased sensitivity of dopamine D 2 receptors results in the development of cocaine CPP at a subthreshold dose of cocaine (Merritt and Bachtell, 2013). It is unclear whether the increase in dopamine D 2 receptors reflects changes in presynaptic D 2 receptors on dopamine terminals, the postsynaptic D 2 receptors on medium spiny neurons, or both.…”

Section: Discussionmentioning

confidence: 99%

Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

O’Neill

Levis

Schreiner

et al. 2014

Neuropsychopharmacol

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Caffeine is the most commonly used psychoactive substance, and consumption by adolescents has risen markedly in recent years. We identified the effects of adolescent caffeine consumption on cocaine sensitivity and determined neurobiological changes within the nucleus accumbens (NAc) that may underlie caffeine-induced hypersensitivity to cocaine. Male Sprague-Dawley rats consumed caffeine (0.3 g/l) or water for 28 days during adolescence (postnatal day 28-55; P28-P55) or adulthood (P67-P94). Testing occurred in the absence of caffeine during adulthood (P62-82 or P101-121). Cocaine-induced and quinpirole (D 2 receptor agonist)-induced locomotion was enhanced in rats that consumed caffeine during adolescence. Adolescent consumption of caffeine also enhanced the development of a conditioned place preference at a sub-threshold dose of cocaine (7.5 mg/kg, i.p.). These behavioral changes were not observed in adults consuming caffeine for an equivalent period of time. Sucrose preferences were not altered in rats that consumed caffeine during adolescence, suggesting there are no differences in natural reward. Caffeine consumption during adolescence reduced basal dopamine levels and augmented dopamine release in the NAc in response to cocaine (5 mg/kg, i.p.). Caffeine consumption during adolescence also increased the expression of the dopamine D 2 receptor, dopamine transporter, and adenosine A 1 receptor and decreased adenosine A 2A receptor expression in the NAc. Consumption of caffeine during adulthood increased adenosine A 1 receptor expression in the NAc, but no other protein expression changes were observed. Together these findings suggest that caffeine consumption during adolescence produced changes in the NAc that are evident in adulthood and may contribute to increases in cocaine-mediated behaviors.

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“…Postsynaptic to dopamine terminals, GABAergic neurons in the striatum integrate dopamine signals in part via complex interactions between D1-and D2-like dopamine receptors (Fontana et al, 1993;Hu and White, 1997;Ikemoto et al, 1997). Thus, transient overexpression of D1 and D2 dopamine receptors during periadolescence (eg Teicher et al, 1995) and altered receptor coupling with cAMP (Andersen, 2002) may regulate responsiveness to cocaine.…”

Section: Discussionmentioning

confidence: 99%

Behavioral and Neurochemical Responses to Cocaine in Periadolescent and Adult Rats

Frantz

O’Dell

Parsons

2006

Neuropsychopharmacol

120

139

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Although recreational drug use by human adolescents is a well-known and long-standing problem, relatively little is known regarding differences in behavioral and physiological responses to abused substances in adolescent vs adult animals. The present study compared effects of the psychomotor stimulant, cocaine, in periadolescent (postnatal days 37-52) and adult (postnatal days 75-90) male Wistar rats. Locomotion and motor stereotypy were recorded after acute and repeated cocaine injections (0, 10, or 20 mg/kg cocaine, intraperitoneal (i.p.), four injections spaced 5 days apart). Spontaneous acquisition of intravenous (i.v.) cocaine self-administration was investigated in two dose groups (B0.37 or 0.74 mg/kg/infusion) over 14 days. Dopamine levels in the nucleus accumbens were recorded under basal conditions (no net flux method) and after cocaine administration (B0.37, 0.74, and 2.92 mg/kg/i.v. infusion or 20 mg/kg i.p.) using in vivo microdialysis. The locomotor data are in partial agreement with previous reports of hyposensitivity to acute cocaine in periadolescent vs adult rats; periadolescents were less active overall than adults. Moreover, adult rats exhibited significant locomotor sensitization after repeated injection of 10 mg/kg cocaine, whereas periadolescents required the high dose of 20 mg/kg cocaine to demonstrate sensitization. Neither age group showed sensitization of motor stereotypies. No age-related difference was observed in acquisition of cocaine self-administration, or in basal or cocaine-stimulated nucleus accumbens dopamine. These experiments imply a developmental dissociation between the motor activating and reinforcing effects of cocaine. Similarities in dopamine levels across age groups suggest that age-specific motor responses to cocaine are not mediated by dopamine in the nucleus accumbens. Neuropsychopharmacology (2007) 32, 625-637.

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The role of D1 and D2 dopamine receptors in the acquisition and expression of cocaine-induced conditioned increases in locomotor behavior

Cited by 53 publications

References 0 publications

Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D₅Receptor-Dependent Redistribution of NMDA Receptors

Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D₅Receptor-Dependent Redistribution of NMDA Receptors

Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

Behavioral and Neurochemical Responses to Cocaine in Periadolescent and Adult Rats

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The role of D1 and D2 dopamine receptors in the acquisition and expression of cocaine-induced conditioned increases in locomotor behavior

Cited by 53 publications

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Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D5Receptor-Dependent Redistribution of NMDA Receptors

Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D5Receptor-Dependent Redistribution of NMDA Receptors

Effects of Adolescent Caffeine Consumption on Cocaine Sensitivity

Behavioral and Neurochemical Responses to Cocaine in Periadolescent and Adult Rats

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Product

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Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D₅Receptor-Dependent Redistribution of NMDA Receptors

Cocaine Enhances NMDA Receptor-Mediated Currents in Ventral Tegmental Area Cells via Dopamine D₅Receptor-Dependent Redistribution of NMDA Receptors