ArticlesSensitization to the Behavioral Effects of Cocaine: Modulation by Dynorphin and κ-Opioid Receptor Agonists
Section snippets
Modulation of mesolimbic dopamine neurotransmission by κ-opioid receptor ligands
Evidence indicating interactions between mesolimbic DA neurons and neurons containing the opioid peptide dynorphin, the postulated endogenous ligand for the κ-opioid receptor [3], has been derived from both anatomical and neurochemical studies. A moderate density of κ-opioid receptors is found in the ventral tegmental area and the core of the nucleus accumbens, whereas a high density of κ-opioid receptors is found in the dorsomedial shell of the NAC 33, 39. Nerve terminals containing dynorphin
Influence of κ-opioid receptor agonists upon the development of sensitization to cocaine: behavioral studies
In view of the interactions between DA and κ-opioid receptor systems, our laboratory has sought to determine whether pharmacological manipulations of these systems can modify psychostimulant-induced behavioral sensitization. Recent studies examining the interaction of κ-opioid receptor agonists with cocaine suggest that this is the case. Heidbreder et al. 12, 13evaluated the locomotor stimulatory effects of cocaine in animals that had received once-daily injections of cocaine (10.0–30.0
Influence of κ-opioid receptor agonists upon cocaine-induced alterations in extracellular dopamine
Two microdialysis studies 5, 32have examined the influence of κ-agonist administration upon the response of mesolimbic DA neurons to an acute cocaine challenge. Both studies have found that administration of the κ-opioid receptor U50488 ca. 20 min prior to an acute cocaine challenge significantly inhibits cocaine-induced DA overflow. Indeed, such findings are not unexpected in view of the inhibitory effects of κ-opioid receptor agonists on basal DA release [10]. Interestingly, however, the
Influence of repeated cocaine administration upon endogenous opioid peptide systems
DA neurons have been shown to regulate dynorphin gene expression in the mammalian central nervous system. Stimulation of DA receptors by the D1–D2 dopamine receptor agonist apomorphine increases dynorphin immunoreactivity and prodynorphin mRNA in both the striatum and the NAC 30, 31. In contrast, the chronic blockade of D1 DA receptors decreases prodynorphin gene expression and tissue levels of dynorphin 7, 35, 36.
Pronounced changes in dynorphin gene expression are also observed in response to
Conclusions
Several studies have shown that κ-opioid receptor agonists can prevent the development of behavioral sensitization to cocaine as well as those changes in mesolimbic DA neurotransmission that occur in response to repeated administration of this agent. It is also apparent that repeated administration of cocaine and other psychostimulants can profoundly affect the activity of endogenous κ-opioid systems. κ-Opioid receptors within the NAC are increased 19, 57, prodynorphin gene expression is
References (66)
- et al.
A10 somatodendritic dopamine autoreceptor sensitivity following withdrawal from repeated cocaine treatment
Neurosci. Lett.
(1990) - et al.
Elevation of striatal and accumbal preproenkephalin, preprotachykinin and preprodynorphin mRNA abundance subsequent to NMDA receptor blockade with MK-801
Mol. Brain Res.
(1995) - et al.
Cocaine binges differentially alter striatal preprodynorphin and zif/268 mRNAs
Mol. Brain Res.
(1995) - et al.
Pre-exposure sensitizes rats to the rewarding effects of cocaine
Pharmacol. Biochem. Behav.
(1990) - et al.
Cocaine self-administration differentially alters mRNA expression of striatal peptides
Mol. Brain Res.
(1992) - et al.
Dopamine transmission in the initiation and expression of drug and stress induced sensitization
Brain Res. Rev.
(1991) - et al.
Blockade of ‘reverse-tolerance’ to cocaine and amphetamine by MK-801
Life Sci.
(1989) - et al.
3H]U69593, a highly selective ligand for the κ-opioid receptor
Eur. J. Pharmacol.
(1985) - et al.
Properties of a selective kappa agonist U-50488H
Life Sci.
(1982) - et al.
Influence of nigrostriatal dopaminergic tone on the biosynthesis of dynorphin and enkephalin in rat stratum
Mol. Brain Res.
(1990)
Regulation of the concentration of dynorphin A1–8 in the striatonigral pathway by the dopaminergic system
Brain Res.
U50,488, a κ opioid receptor agonist, attenuates cocaine-induced increases in extracellular dopamine in the nucleus accumbens
Neurosci. Lett.
Dual inhibitory action of enadoline (CI977) on release of amino acids in the rat hippocampus
Eur. J. Pharmacol.
Dopaminergic regulation of striatal proenkephalin mRNA and prodynorphin mRNAContrasting effects of D1 and D2 antagonists
Neuroscience
Selectivity of various opioid peptides towards delta-, kappa-, and mu-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the brain
Neuropeptides
Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration
Brain Res.
Cellular substrates for interactions between dynorphin terminals and dopamine dendrites in rat ventral area and substantia nigra
Brain Res.
The neural basis of drug-cravingAn incentive–sensitization theory of addiction
Brain Res. Rev.
N-Methyl-d-aspartate receptors mediate dopamine-induced changes in extrapyramidal and dynorphin systems
Brain Res.
Acute amphetamine or methamphetamine alters opioid peptide mRNA expression in rat striatum
Mol. Brain Res.
“Binge” cocaine administration induces a sustained increase of prodynorphin mRNA in rat caudate-putamen
Mol. Brain Res.
Systemic administration of dynorphin A [1–13]inhibits different behavioral responses induced by cocaine in the mouse
Neuropharmacology
Amphetamine administered to the ventral tegmental area but not to the nucleus accumbens sensitizes rats to systemic morphineLack of conditioned effects
Brain Res.
Dynorphin is a specific endogenous ligand of the κ-opioid receptor
Science
The opioid peptide dynorphin directly blocks NMDA receptor channels in the rat
J. Physiol.
Microdialysis and behavioral evidence of the functional antagonism of cocaine by the kappa agonist U50488
Acute and chronic cocaine binging differentially alter striatal opioid and nuclear transcription factor mRNAs
Synapse
Cocaine self-administration increases prodynorphin, but not c-fos mRNA in rat striatum
NeuroReport
Differential involvement of ventral tegmental mu, delta and kappa opioid receptors in modulation of basal mesolimbic dopamine releaseIn vivo microdialysis studies
J. Pharmacol. Exp. Ther.
Opposite effects of μ- and κ-opioid agonists on dopamine release in the nucleus accumbens and dorsal caudate of freely-moving rats
J. Pharmacol. Exp. Ther.
Conditioned responses to cocaine-related stimuli in cocaine abuse patients
Psychopharmacology
Development of behavioral sensitization to cocaineInfluence of kappa opioid receptor agonists
J. Pharmacol. Exp. Ther.
The kappa opioid receptor agonist U-69593 attenuates cocaine-induced behavioral sensitization in the rat
Brain Res.
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