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R C Pierce

Publications and source records attributed to R C Pierce.

At least 19 recordsLinked to original sources
PubMed2006

Cooperative activation of D1-like and D2-like dopamine receptors in the nucleus accumbens shell is required for the reinstatement of cocaine-seeking behavior in the rat.

Activation of D1-like (D1, D5) or D2-like (D1, D3, D4) dopamine receptors in the nucleus accumbens shell is sufficient to reinstate cocaine-seeking behavior in rats. The goal of these experiments was to assess whether cooperative activation of D1-like and D2-like dopamine receptors in the accumbens shell is required to promote cocaine reinstatement. Rats were initially trained to self-administer cocaine (0.25 mg, i.v.) using a fixed-ratio schedule of reinforcement for approximately 21 days. Animals subsequently underwent an extinction phase during which saline was substituted for cocaine. Once cocaine self-administration behavior was extinguished (defined as <15% of the total responses maintained during self-administration), dopamine receptor agonist-induced reinstatement of cocaine seeking was assessed. Administration of the selective D1/5 agonist R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF-81297) (1.0 microg) or the D2/3 receptor agonist trans-(-)-(4aR)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g]quinoline hydrochloride (quinpirole) (3.0 microg) directly into the nucleus accumbens shell promoted reinstatement of cocaine seeking. In order to determine if endogenous dopamine tone in the accumbens shell is required for dopamine receptor agonist-induced reinstatement of cocaine seeking, D1/5 or D2/3 dopamine receptor antagonists were administered into the nucleus accumbens shell prior to a selective dopamine receptor agonist. Microinfusion of the D2/3 dopamine receptor antagonist sulpiride ((S)-5-aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2-methoxybenzamide) (1.0 microg) into the nucleus accumbens shell 10 minutes prior to SKF-81297 (1.0 microg) blocked the ability of this D1-like dopamine receptor agonist to reinstate cocaine seeking. Similarly, administration of the selective D1/5 dopamine receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH-23390) (1.0 microg) into the nucleus accumbens shell prior to quinpirole (3.0 microg) blocked reinstatement of drug-seeking behavior elicited by this D2/3 dopamine receptor agonist. Moreover, intra-accumbal shell co-administration of subthreshold doses of quinpirole (1.5 microg) and SKF-81297 (0.1 microg) promoted cocaine-seeking behavior. Collectively, these results indicate that cooperative activation of D1-like and D2-like dopamine receptors in the nucleus accumbens shell is necessary to reinstate cocaine seeking in rats.

Animals↗
PubMed2005

D1-like and D2 dopamine receptor antagonists administered into the shell subregion of the rat nucleus accumbens decrease cocaine, but not food, reinforcement.

Cocaine self-administration experiments were designed to assess the respective roles of D1-like and D2-like dopamine receptors in the ventral forebrain in cocaine reinforcement. D1-like or D2-like dopamine receptor antagonists were microinjected into the nucleus accumbens core, nucleus accumbens shell, neostriatum or lateral septum prior to sessions in which cocaine was self-administered under a progressive ratio schedule by rats. The results indicated that administration of a D1/5 (SCH-23390) or a D2/D3/D4 (eticlopride), but not a D3 (U99194A) or D4 (L-750,667), dopamine receptor antagonist into the core and shell of the nucleus accumbens decreased the reinforcing efficacy of cocaine. However, in control experiments intra-accumbal core administration of SCH-23390 or eticlopride decreased food self-administration, whereas administration of these drugs into the accumbens shell had no effect on food reinforcement. Neither SCH-23390 nor eticlopride influenced cocaine reinforcement when administered into the neostriatum or lateral septum. Collectively, these results indicate that D1-like and D2 dopamine receptors in the nucleus accumbens shell selectively modulate the reinforcing efficacy of cocaine, whereas D1-like and D2 dopamine receptors in the accumbens core have a more general influence on reinforced behaviors.

Animals↗
PubMed2005

Cocaine-induced alterations in dopamine receptor signaling: implications for reinforcement and reinstatement.

The transition from casual drug use to addiction, and the intense drug craving that accompanies it, has been postulated to result from neuroadaptations within the limbic system caused by repeated drug exposure. This review will examine the implications of cocaine-induced alterations in mesolimbic dopamine receptor signaling within the context of several widely used animal models of addiction. Extensive evidence indicates that dopaminergic mechanisms critically mediate behavioral sensitization to cocaine, cocaine-induced conditioned place preference, cocaine self-administration, and the drug prime-induced reinstatement of cocaine-seeking behavior. The propagation of the long-term neuronal changes associated with recurring cocaine use appears to occur at the level of postreceptor signal transduction. Repeated cocaine treatment causes an up-regulation of the 3',5'-cyclic adenosine monophosphate (cAMP)-signaling pathway within the nucleus accumbens, resulting in a dys-regulation of balanced D1/D2 dopamine-like receptor signaling. The intracellular events arising from enhanced D1-like postsynaptic signaling mediate both facilitatory and compensatory responses to the further reinforcing effects of cocaine.

Animals↗
PubMed2003

Tyrosine kinase B and C receptors in the neostriatum and nucleus accumbens are co-localized in enkephalin-positive and enkephalin-negative neuronal profiles and their expression is influenced by cocaine.

Single- and double-label immunohistochemistry were used to determine the extent to which the tyrosine kinase B and C receptors, are expressed in enkephalin-immunopositive or enkephalin-immunonegative neuronal profiles in the rat neostriatum and nucleus accumbens. Results indicate that tyrosine kinase B and C receptors are co-localized in both enkephalin-positive and enkephalin-negative neurons in both of these nuclei, which suggests that these receptors influence both the striatal-pallidal (enkephalin) and striatal-ventral mesencephalic (substance P/dynorphin) pathways. We also examined the influence of acute or repeated injections of cocaine on the number of tyrosine kinase B and C receptors immunoreactive neuronal profiles in the rat neostriatum and nucleus accumbens. Following an acute injection of cocaine (15 mg/kg, i.p.), there were significant decreases in the number of tyrosine kinase B and C receptors immunoreactive profiles in specific regions of the neostriatum and nucleus accumbens relative to saline-pretreated rats. One or 14 days following the last of seven daily injections of 15 mg/kg cocaine or saline there were no differences in the numbers of tyrosine kinase B or C receptors immunoreactive neuronal profiles between these treatment groups.Collectively, the present results indicate that tyrosine kinase B and C receptors in the neostriatum and nucleus accumbens are co-localized in enkephalin-positive and enkephalin-negative neuronal profiles, which suggests that the striatal medium spiny neurons expressing tyrosine kinase B and C receptors include those that project to the pallidum or the ventral mesencephalon. The current results also show that an acute injection of cocaine results in a decrease in the number of tyrosine kinase B and C receptors immunoreactive neuronal profiles in specific regions of the nucleus accumbens and neostriatum, indicating that cocaine-induced increases in extracellular dopamine in the striatal complex result in compensatory decreases in the expression of tyrosine kinase B and C receptors.

Animals↗
PubMed2003

Inhibition of NMDA-induced striatal dopamine release and behavioral activation by the neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate.

Our laboratory has previously shown that the synthetic neuroactive steroid 3alpha-hydroxy-5beta-pregnan-20-one hemisuccinate (3alpha5betaHS) is a negative modulator of NMDA receptors in vitro. Similarly, 3alpha5betaHS exhibits rapid sedative, analgesic, anticonvulsive, and neuroprotective effects in vivo. Here we report a study designed to investigate whether a negatively charged neuroactive steroid, 3alpha5betaHS, modulates the action of NMDA receptors in vivo. Our results indicate that peripherally administered 3alpha5betaHS enters the CNS and inhibits NMDA-mediated motor activity and dopamine release in the rat striatum. The increase in motor activity induced by intrastriatal microinjection of NMDA was blocked by the systemic administration of 3alpha5betaHS and the NMDA-induced increase in extracellular dopamine in the striatum was also attenuated by both systemically administered and intrastriatally administered (by in vivo microdialysis) 3alpha5betaHS. These data indicate that 3alpha5betaHS acts through striatal NMDA receptors in vivo. When taken together, these results suggest that neuroactive steroids may prove to be effective in the treatment of neurological and psychiatric disorders involving over-stimulation of NMDA receptors in the mesotelencephalic dopamine system.

Animals↗
PubMed2002

Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens.

One of the major determinants of reinstatement to cocaine use among human addicts is acute reexposure to the drug, which often precipitates cocaine craving and relapse. We used an animal model of cocaine relapse to determine the role of the glutamatergic pathway from the medial prefrontal cortex (mPFC) to the nucleus accumbens in the reinstatement of cocaine-seeking behavior after a cocaine priming injection. Rats were trained to self-administer cocaine intravenously on a second order schedule. Responding was extinguished subsequently by substituting saline for cocaine. During subsequent reinstatement sessions, drug-seeking behavior was assessed after noncontingent priming injections. Results indicated that reinstatement induced by a systemic cocaine injection was blocked by intra-mPFC administration of the dopamine antagonist flupenthixol. Consistent with this finding, administration of cocaine directly into the mPFC reinstated cocaine-seeking behavior. Administration of cocaine into the nucleus accumbens also reinstated drug seeking, whereas microinjection of cocaine into the neostriatum or lateral septum did not. Reinstatement of cocaine seeking induced by intra-mPFC cocaine was blocked by administration of the AMPA receptor antagonist CNQX into the nucleus accumbens. Administration of the NMDA receptor antagonist AP-5 into the nucleus accumbens had variable effects on reinstatement induced by intra-mPFC cocaine in that AP-5 had no effect in some animals but augmented reinstatement in others. Subsequent experiments showed that intra-accumbal microinjection of AP-5 alone dose-dependently reinstated cocaine seeking. These data indicate that the glutamatergic pathway from the mPFC to the nucleus accumbens plays an important role in cocaine priming-induced reinstatement of drug seeking. Moreover, the present results demonstrate that AMPA and NMDA receptors in the nucleus accumbens have opposing roles in the reinstatement of cocaine-seeking behavior.

Anesthetics, Local↗
PubMed2001

OLETF (Otsuka Long-Evans Tokushima Fatty) rats that lack the CCK 1 (A) receptor develop less behavioral sensitization to repeated cocaine treatment than wild type LETO (Long Evans Tokushima Otsuka) rats.

OLETF (Otsuka Long-Evans Tokushima Fatty) lacking the CCK 1 (A) receptor have similar spontaneous activity and locomotor response (horizontal and vertical activity) in response to a single injection of cocaine as the wild type LETO (Long Evans Tokushima Otsuka) rats. In contrast, the OLETF rats display more stereotypy in response to the first dose of cocaine than the LETO rats. Tested at 7 and 14 days after a one week daily treatment with cocaine, the LETO rats display robust behavioral sensitization to cocaine while the OLETF rats did not. These results support the hypothesis that endogenous CCK released by cocaine treatment and acting at CCK 1 receptors is required for the development and/or expression of this behavior.

Animals↗
PubMed2001

The role of neurotrophic factors in psychostimulant-induced behavioral and neuronal plasticity.

Several neurotrophic factors influence the development, maintenance and survival of dopaminergic neurons in the mammalian central nervous system (CNS), including neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), basic fibroblast growth factor (bFGF) and glial derived neurotrophic factor (GDNF). This review focuses on the role of these neurotrophic factors in psychostimulant-induced behavioral sensitization, a form of dopamine-mediated neuronal plasticity that models aspects of paranoid schizophrenia as well as drug craving among psychostimulant addicts. Whereas NT-3, CNTF and bFGF appear to play a positive role in psychostimulant-induced behavioral sensitization, GDNF inhibits this form of behavioral plasticity. The role of BDNF in behavioral sensitization, however, remains elusive. While it has been shown that neurotrophic factors can influence the behavioral, structural and biochemical phenomena related to psychostimulant-induced neuronal plasticity, it is unclear which neurotrophic factors are important physiologically and which have purely pharmacological effects. In either case, examining the role of neurotrophic factors in behavioral sensitization may enhance our understanding of the mechanisms underlying the development of paranoid psychosis and drug craving and lead to the development of novel pharmacological treatments for these disorders.

Animals↗
PubMed2000

Repeated stimulation of L-type calcium channels in the rat ventral tegmental area mimics the initiation of behavioral sensitization to cocaine.

RATIONALE: A substantial body of evidence indicates that ion flux through L-type calcium channels and N-methyl-D-aspartate (NMDA) receptors contributes to behavioral sensitization to cocaine. OBJECTIVES: The following experiments were designed to evaluate the role of calcium influx through L-type calcium channels or NMDA receptors in the ventral tegmental area (VTA) in the initiation of behavioral sensitization to cocaine. METHODS: The L-type calcium channel agonist BayK 8644, the glutamate agonist NMDA, or vehicle was microinjected into the VTA on 3 consecutive days. Following a 2-week withdrawal period, all rats received a challenge injection of cocaine (15 mg/kg, i.p.) in order to assess potential cross-sensitization with the NMDA or BayK 8644 pretreatments. RESULTS: Repeated intra-VTA microinjections of BayK 8644, but not NMDA, resulted in an augmentation of the behavioral response to cocaine. CONCLUSIONS: These results indicate that calcium influx through L-type calcium channels produces neurophysiological adaptations that mimic those resulting from intermittent exposure to cocaine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1999

Neurotrophin-3 contributes to the initiation of behavioral sensitization to cocaine by activating the Ras/Mitogen-activated protein kinase signal transduction cascade.

These experiments were designed to assess the role of neurotrophins and the Ras/mitogen-activated protein kinase (MAP) signal transduction cascade in behavioral sensitization to cocaine. The first experiments evaluated the effect of three daily intra-ventral tegmental area (VTA) microinjections of neurotrophin-3 (NT-3) or brain-derived neurotrophic factor (BDNF) on the behavioral-activating effects of a subsequent challenge injection of cocaine in rats. Results indicated that, although NT-3 did not influence behavior across the three microinjection days, animals displayed a sensitized behavioral response to the subsequent cocaine challenge injection. In contrast, BDNF microinjections resulted in a progressive increase in behavioral activity but did not influence the subsequent behavioral response to cocaine. A second series of experiments assessed the effect of inhibiting the MAP kinase signal transduction cascade on the initiation of behavioral sensitization to cocaine. The MAP kinase kinase inhibitor PD98059, or its vehicle, was microinjected into the VTA before three daily cocaine injections. Although PD98059 did not influence the acute behavioral response to cocaine, it blocked sensitization. Finally, the effects of acute and repeated cocaine injections on NT-3 and BDNF mRNA levels in the VTA, substantia nigra, and hippocampus were assessed. Results indicated that an acute cocaine injection resulted in a transient increase in NT-3 mRNA levels in the VTA. Collectively, these results suggest that NT-3 contributes to the initiation of behavioral sensitization to cocaine by activating the Ras/MAP kinase signal transduction system. The present data also indicate that BDNF itself produced a progressive augmentation in behavioral activation with repeated administration.

Animals↗
PubMed1999

The monoamine neurons of the rat brain preferentially express a splice variant of alpha1B subunit of the N-type calcium channel.

The N-type voltage-dependent calcium channels play a significant role in neurotransmitter release. The alpha1B subunit of the N-type calcium channel functions as the primary subunit that forms the pore and contains the structural motifs that mediate the pharmacological and gating properties of the channel. We report on an isoform of the alpha1B subunit that is preferentially expressed by the monoaminergic neurons of the rat brain. This isoform contains a 21-amino acid cassette in the synprint site present in the cytoplasmic loop between domains IIS6 and IIIS1. RT-PCR of micropunched tissue was used to show preferential expression of this isoform in regions of the brain containing monoaminergic neurons and to a lesser extent in the cerebellum. Double-label in situ hybridization was used to show expression of this isoform mRNA in dopaminergic neurons of the ventral mesencephalon. The expression of two distinct N-type calcium channels containing these alpha1B subunit isoforms by the monoaminergic neurons may provide for synapse-specific regulation of neurotransmitter release.

Alternative Splicing↗
PubMed1998

Ibotenic acid lesions of the dorsal prefrontal cortex disrupt the expression of behavioral sensitization to cocaine.

The present study determined the effect of bilateral lesions of specific cortical or thalamic nuclei that provide excitatory amino acid afferents to the nucleus accumbens (i.e. the dorsal prefrontal cortex, ventral prefrontal cortex, amygdala, hippocampus and periventricular thalamus) on the expression of cocaine-induced behavioral sensitization. Lesions of these nuclei were made during a three-week withdrawal period following repeated daily injections of cocaine or saline. The results indicate that dorsal prefrontal cortex lesions block the expression of behavioral sensitization to cocaine, while ventral prefrontal cortex, fimbria fornix, amygdala and thalamic lesions have no effect. A subsequent microdialysis experiment was performed in order to evaluate the effect of dorsal prefrontal cortex lesions on glutamate transmission in the nucleus accumbens core of cocaine- and saline-pretreated rats. The systemic injection of cocaine produced a significant increase in extracellular glutamate in the nucleus accumbens core among animals with a sham surgery; this effect was blocked by a bilateral lesion of the dorsal prefrontal cortex. Taken together, these results indicate that the dorsal prefrontal cortex, which provides excitatory amino acid input selectively to the core region of the nucleus accumbens, enhances the expression of behavioral sensitization to cocaine by increasing glutamate transmission in this subnucleus.

Animals↗
PubMed1998

A role for sensitization in craving and relapse in cocaine addiction.

Sensitization to cocaine refers to the behavioral model of cocaine addiction where the motor stimulant effect of cocaine is augmented for months after discontinuing a regimen of repeated cocaine injections. There has been speculation that the neuroadaptations mediating this sensitization phenomenon may, in part, underlie the behavioral changes produced by chronic cocaine abuse, including paranoia, craving and relapse. Criteria are proposed that may assist in determining which neuroadaptations are most relevant in this regard. Using these criteria, a model is presented that endeavors to incorporate neuroadaptations issuing directly from the pharmacological effects of cocaine and those arising from learned associations the organism makes with the cocaine injection procedure and pharmacological actions. It is proposed that the pharmacological neuroadaptations predominate in the manifestation of cocaine-induced paranoia, while the changes derived from learning may provide more critical underpinnings for cocaine craving and relapse.

Behavior↗
PubMed1998

Calcium-mediated second messengers modulate the expression of behavioral sensitization to cocaine.

To assess the influence of calcium channel antagonists on the expression of behavioral sensitization to cocaine, the L-type calcium channel antagonist diltiazem or the N-type calcium channel antagonist omega-conotoxin GVIA was microinjected into the medial nucleus accumbens before a systemic cocaine challenge injection among rats that were previously treated with daily systemic saline or cocaine injections. The results indicated that both of these drugs attenuated the expression of behavioral sensitization to cocaine. Among saline-pretreated rats, diltiazem did not influence the behavioral response to an acute injection of cocaine, whereas omega-conotoxin significantly impaired acute cocaine-induced behavioral hyperactivity. A second series of experiments assessed the influence of protein kinases on the expression of behavioral sensitization to cocaine. Inhibitors of calcium/calmodulin-dependent protein kinase II (KN-93, N-[2-[[[3-(4'-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-( 2-hydroxyethyl)-4'-methoxy-benzenesulfonamide phosphate), protein kinase A (H-89, N-[2((p-bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide) or calcium-dependent protein kinase C (bisindolymaleimide I, 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimi de) were microinjected into the medial nucleus accumbens before a challenge injection of cocaine among rats repeatedly administered either saline or cocaine. None of the kinase inhibitors influenced the behavioral response induced by cocaine in saline-pretreated rats. Among cocaine-sensitized animals, the microinjection of KN-93 or bisindolymaleimide I blocked the expression of behavioral sensitization to cocaine, whereas H-89 had no effect. Taken together, these results indicate that neuronal calcium, acting via calcium-dependent kinases, promotes the expression of behavioral sensitization to cocaine.

Animals↗
PubMed1997

NAC-1, a rat brain mRNA, is increased in the nucleus accumbens three weeks after chronic cocaine self-administration.

Chronic cocaine use leads to biochemical and behavioral changes that can persist for weeks to months after drug administration is discontinued. Alterations in gene expression in the mammalian CNS may contribute to these long-term neural consequences of cocaine abuse. A combined in situ transcription-PCR amplification strategy was used to isolate a novel mRNA, NAC-1, from the nucleus accumbens of rats 3 weeks after discontinuing 3 weeks of intravenous cocaine self-administration. In rats that self-administered cocaine, levels of NAC-1 were increased approximately 50% in the nucleus accumbens but not in the dorsal striatum or hippocampus, when compared with levels from yoked-saline controls. In situ hybridization analysis demonstrated increased numbers of NAC-1-expressing cells in the nucleus accumbens of rats who had self-administered cocaine. NAC-1 mRNA exists as one form, approximately 4400 nucleotides (nt) in size, and also is present at much lower amounts in non-neural tissues. A full-length cDNA clone was isolated from a whole brain library. The predicted polypeptide sequence contains a POZ domain in the first 120 amino acids; the same POZ domain sequence mediates protein-protein interactions among some transcriptional regulators. NAC-1 mRNA levels were also increased in the nucleus accumbens 1 week after 6 d of noncontingent cocaine treatments. Regulation of NAC-1 mRNA in the nucleus accumbens demonstrates a long-term effect of cocaine use on cellular function that may be relevant in behavioral sensitization or cocaine self-administration.

Amino Acid Sequence↗
PubMed1997

Repeated cocaine modifies the mechanism by which amphetamine releases dopamine.

This study determined whether daily cocaine administration initiates a calcium requirement for the increase in extracellular dopamine produced by psychostimulants. The increase in extracellular dopamine induced by perfusion of amphetamine through a microdialysis probe in the nucleus accumbens shell was enhanced in cocaine- relative to saline-pretreated rats. The augmented portion of the amphetamine-induced increase in nucleus accumbens dopamine was abolished by the coperfusion of L- or N-type calcium channel blockers. Inhibition of calcium/calmodulin-dependent protein kinase II (CaM-KII) also prevented the augmented increase in dopamine by amphetamine, whereas inhibition of vesicular exocytosis by botulinum toxin B was ineffective. When the concentration of extracellular dopamine in the nucleus accumbens was elevated by blocking the plasmallemal dopamine transporter with GBR-12909, the augmented increase in extracellular dopamine in rats sensitized to repeated cocaine was blocked by a CaM-KII inhibitor. Pretreatment with botulinum toxin B prevented the increase in extracellular dopamine by GBR-12909 in both cocaine-pretreated and control rats. Taken together, these results demonstrate that the psychostimulant-induced enhanced increase in extracellular dopamine in the nucleus accumbens shell of cocaine-pretreated rats arises from the induction of calcium- and CaM-KII-dependent mechanisms.

Amphetamine↗
PubMed1997

The NMDA antagonist, dizocilpine, enhances cocaine reinforcement without influencing mesoaccumbens dopamine transmission.

In order to assess the role of excitatory amino acids (EAAs) in the reinforcing property of cocaine, the NMDA antagonist, dizocilpine, or the AMPA antagonist, DNQX, were administered to animals previously trained to self-administer cocaine (1.0, 0.4 or 0.16 mg/kg per infusion). The highest doses of dizocilpine (0.1 mg/kg, IP) and DNQX (30 mg/kg, IP) significantly reduced operant responding for cocaine maintained on a fixed ratio schedule of reinforcement. However, whereas dizocilpine had no influence operant responding for food, DNQX significantly decreased lever pressing for this reinforcer. These results indicate that an NMDA antagonist produces a relatively selective enhancement of cocaine reinforcement, while an AMPA antagonist decreases cocaine self-administration only at a dose that also impairs responding for an alternate reinforcer. A parallel in vivo microdialysis study performed in freely moving rats tested the effects of dizocilpine alone and in combination with cocaine on extracellular dopamine in the nucleus accumbens shell. The results revealed that dizocilpine alone (0.1 mg/kg, IP) did not alter basal extracellular dopamine levels in the nucleus accumbens or spontaneous behavior. In addition, 0.1 mg/kg dizocilpine did not alter the increase in dopamine in the accumbens shell or behavioral hyperactivity produced by cocaine (15 or 30 mg/kg). Collectively, these findings suggest that dizocilpine enhances the reinforcing effect of cocaine without influencing dopamine transmission in the nucleus accumbens shell.

Animals↗