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B M Cox

Publications and source records attributed to B M Cox.

At least 19 recordsLinked to original sources
PubMed2001

Chronic GBR 12909 administration differentially alters prodynorphin gene expression compared to cocaine.

The effect of the selective dopamine uptake inhibitor 1-[2-[bis(4-flourophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride (GBR 12909) was examined on prodynorphin gene expression. GBR 12909 or vehicle was continuously infused for 7 days via osmotic minipump, or injected daily into male rats. Both continuous infusions and daily injections of GBR 12909 produced significant decreases in prodynorphin expression in the hypothalamus (37% and 31% decreases, respectively). There were no significant changes in the caudate putamen, hippocampus or nucleus accumbens. One injection of GBR 12909 had no effects on prodynorphin expression in any of the brain regions studied, suggesting that the effect in the hypothalamus is not an acute effect. As previously reported for other treatment regimens, continuous infusion of cocaine produced a 35% significant decrease in the hypothalamus, consistent with the effects of GBR 12909. In contrast to GBR 12909, however, cocaine also produced a significant increase in prodynorphin expression in the caudate putamen. Thus, chronic inhibition of dopamine uptake can regulate prodynorphin expression in the hypothalamus. In contrast, the increase in the caudate putamen following cocaine administration may not be related to the inhibition of dopamine uptake, since it was not produced by a selective dopamine uptake inhibitor. These findings suggest that regulation of prodynorphin gene expression by cocaine in the caudate putamen may be mediated by the inhibition of norepinephrine or serotonin uptake, by a combination of effects on two or three monoamine transporters, or by a mechanism unrelated to transporter inhibition.

Animals↗
PubMed2000

Immunoprecipitation of high-affinity, guanine nucleotide-sensitive, solubilized mu-opioid receptors from rat brain: coimmunoprecipitation of the G proteins G(alpha o), G(alpha i1), and G(alpha i3).

Antibodies directed against the C-terminal and the N-terminal regions of the mu-opioid receptor were generated to identify the G proteins that coimmunoprecipitate with the mu receptor. Two fusion proteins were constructed: One contained the 50 C-terminal amino acids of the mu receptor, and the other contained 61 amino acids near the N terminus of the receptor. Antisera directed against both fusion proteins were capable of immunoprecipitating approximately 70% of solubilized rat brain mu receptors as determined by [3H][D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin ([3H]DAMGO) saturation binding. The material immunoprecipitated with both of the antisera was recognized as a broad band with a molecular mass between 60 and 75 kDa when screened in a western blot. Guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) had an EC50 of 0.4 nM in diminishing [3H]DAMGO binding to the immunoprecipitated pellet. The ratio of G proteins to mu receptors in the immunoprecipitated material was 1:1. When the material immunoprecipitated with affinity-purified antibody was screened for the presence of G protein a subunits, it was determined that G(alpha)o, G(alpha)i1, G(alpha)i3, and to a lesser extent G(alpha)i2, but not G(alpha)s or G(alpha)q11, were coimmunoprecipitated with the mu receptor. Inclusion of GTPgammaS during the immunoprecipitation process abolished the coimmunoprecipitation of G proteins.

Animals↗
PubMed1999

Regulation of nociceptin/orphanin FQ gene expression by neuropoietic cytokines and neurotrophic factors in neurons and astrocytes.

We have identified the gene encoding nociceptin/orphanin FQ (N/OFQ), the novel opioid-like neuropeptide, as responsive to ciliary neurotrophic factor (CNTF). N/OFQ mRNA levels were induced five- and ninefold by CNTF in striatal and cortical neurons. In primary astrocytes CNTF also increased N/OFQ mRNA levels. CNTF is a multifunctional cytokine that mediates the development and differentiation of both neurons and astrocytes and supports the survival of various neurons. CNTF is also an injury-induced factor in the brain playing a crucial role in astrogliosis. The mechanism by which CNTF elicits these effects is not well understood, but it is likely to involve regulation of specific genes. CNTF regulation of N/OFQ expression was sensitive to the kinase inhibitors H-7 and genistein but not to inhibition of protein synthesis. This pharmacological profile is consistent with CNTF activating the Janus protein tyrosine kinase (JAK)/ signal transducers and activators of transcription (STAT) pathway to induce N/OFQ transcription. In nuclear extracts of CNTF-treated striatal neurons DNA binding of STAT proteins was increased. Radioimmunoassays revealed elevated N/OFQ immunoreactivity in striatal neurons after CNTF treatment. Expression of the related proenkephalin gene was not affected by CNTF in either neuronal or glial cultures. Regulation of N/OFQ expression by CNTF might point to a possible function of N/OFQ during development and after neural injury.

Animals↗
PubMed1998

Ca2+/calmodulin-dependent transcriptional activation of delta-opioid receptor gene expression induced by membrane depolarization in NG108-15 cells.

Regulation of gene expression is one of the mechanisms by which neuronal activity elicits long-term changes in neuronal phenotype and function. Although activity-dependent induction of immediate-early genes has been extensively studied, much less is known about the late-response genes. We have investigated the activity-dependent regulation of delta-opioid receptor (DOR) mRNA levels in NG108-15 cells. Transsynaptic activation was mimicked by depolarization with 55 mM KCl or veratridine. Both treatments lead to a time-dependent increase of DOR mRNA levels. Ca2+ entry through L-type voltage-dependent Ca2+ channels activated by depolarization appears to be involved, because L-type channel blockers reduced the induction of DOR expression. Ca2+ binding to calmodulin is the next step in the signal transduction pathway, because a calmodulin antagonist, W7, reduced the effect of veratridine. A selective inhibitor of calmodulin kinases (KN-62) and cyclosporin, an inhibitor of calcineurin, also antagonized the depolarization-induced increase in DOR mRNA levels, which indicates that both calcium/calmodulin-dependent enzymes are involved in the activity-dependent induction of DOR gene expression. Induction of DOR gene expression by an activity-dependent increase in intracellular Ca2+ concentration may serve as a feedback regulatory mechanism because activation of DOR leads to hyperpolarization and lower excitability of neurons.

Binding Sites↗
PubMed1998

Activity and cyclic AMP-dependent regulation of nociceptin/orphanin FQ gene expression in primary neuronal and astrocyte cultures.

The regulation of nociceptin/orphanin FQ (N/OFQ) gene expression by neuronal activity and by activation of the cyclic AMP signaling pathway in primary neuronal and astroglial cultures is described. Neuronal activity mimicked by veratridine-mediated depolarization profoundly increased N/OFQ gene expression in primary striatal neurons. Calcium entry through L-type, but not N-type, voltage-sensitive calcium channels activated by depolarization appears to be involved, because nitrendipine and nifedipine, but not omega-conotoxin, reduced the induction of N/OFQ expression by veratridine. A selective inhibitor of calcium/calmodulin kinases (KN-62) also antagonized the depolarization-induced increase in N/OFQ mRNA levels, suggesting a role for these enzymes in the activity-dependent induction of N/OFQ gene expression. Constitutively expressed transcription factors may mediate N/OFQ gene expression levels, because veratridine induction of N/OFQ transcription was insensitive to the protein synthesis inhibitor cycloheximide. Regulation of N/OFQ gene expression by depolarization and cyclic AMP is not restricted to striatal neurons, because similar regulation was also observed in neuronal cultures derived from the cerebral cortex. Veratridine did not increase N/OFQ mRNA levels in primary astrocyte cultures; however, elevated intracellular cyclic AMP levels lead to a dramatic, 30-fold induction of N/OFQ mRNA levels in these cells.

Animals↗
PubMed1998

Transient upregulation of mu opioid receptor mRNA levels in nucleus accumbens during chronic cocaine administration.

Chronic continuous cocaine administration for 3 days has been shown to upregulate the level of mu opioid receptor (MOR) mRNA in the nucleus accumbens (n. acc.) of rat brain. Dopamine (DA) antagonists, SCH 23390, eticlopride, and nafadotride, blocked, and DA agonists, SKF 38393, R(+)-6-bromo-APB hydrobromide, and bromocriptine, mimicked the cocaine-induced upregulation of MOR mRNA, suggesting involvement of both subfamilies of DA receptors in the effect of cocaine. In the present study the time course of cocaine-induced and DA agonist induced alterations in the level of MOR mRNA in n. acc. has been determined and compared with the changes in the level of MOR binding sites. Male Sprague-Dawley rats were treated with saline, cocaine (50 mg.kg-1.day-1), or DA agonists for periods between 24 and 336 h. Expression of MOR mRNA in n. acc. was estimated using quantitative competitive polymerase chain reaction assays following reverse transcription. The cocaine-induced upregulation of MOR mRNA in n. acc. was transient, developing 2 days after exposure, and peaking at 3 days with return to baseline levels by 4 days of chronic continuous cocaine treatment. The temporal characteristics of DA agonist induced increase in the levels of MOR mRNA in n. acc. were similar to those of cocaine, with maximum effect after 3 days of treatment. The density of [3H]DAMGO binding sites in n. acc. was 30% higher after 3 days of cocaine administration than in saline-treated control animals, but returned toward baseline levels after 4 days of cocaine treatment. No changes in the binding of [3H]DAMGO were detected after 7 or 14 days exposure to cocaine. The affinity of [3H]DAMGO to n. acc. membranes (approximately 2.0 nM) was unchanged during the cocaine treatment.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

Effect of ethanol drinking on the gene expression of opioid receptors, enkephalinase, and angiotensin-converting enzyme in two inbred mice strains.

There is convincing evidence that genetic factors contribute to the predisposition to alcoholism. In this respect, alcohol-preferring (like C57BL/6 mice) and alcohol-avoiding lines (like DBA/2 mice) of animals served as models in the search for neurobiological substrates of excessive ethanol consumption. One of the systems that is thought to be associated with the incidence of alcoholism is the endogenous opioid system. In the first experiment, basal mRNA levels of mu- and delta-opioid receptors, and of opioid-degrading enzymes enkephalinase (neutral endopeptidase 24.11; NEP) and angiotensin-converting enzyme (ACE) in the brain regions of C57BL/6 and DBA/2 mice did not reveal genetically determined differences in these parameters between the two strains. Furthermore, in the brain regions studied, the corresponding enzyme activities of NEP and ACE did not differ significantly between the lines of mice, except for a higher NEP activity in the striatum and olfactory bulb of DBA/2 mice (p < 0.01). In the second experiment, C57BL/6 and DBA/2 mice were offered a free choice between water and 10% ethanol solution for 4 weeks and were killed thereafter; from another group, ethanol was removed for 3 days and from a third group ethanol was removed for 3 weeks before killing. In the striatum, a highly significant increase in the ACE mRNA amount was detected after 3 weeks of removal of ethanol in C57BL/6 mice, whereas in DBA/2 mice the delta-opioid receptor mRNA level was increased at this time when compared with the corresponding ethanol treatment group. The most striking changes were seen in the hypothalamus, where mu-opioid receptor, ACE, and NEP mRNA amounts markedly decreased after ethanol treatment in both strains. Thus, chronic ethanol intake caused significant changes in the gene expression of distinct components of the endogenous opioid system. These findings further underline an involvement of the opioid system in the effects of ethanol.

Alcohol Drinking↗
PubMed1997

Release of endogenous glutamate and gamma-aminobutyric acid from rat striatal tissue slices measured by an improved method of high performance liquid chromatography with electrochemical detection.

The release of endogenous glutamate and gamma-aminobutyric acid (GABA) from rat brain tissue slices was studied using a tissue slice assay in which detectable amounts of the amino acids were released from 1-2 mg of tissue. An improved method of high performance liquid chromatography (HPLC) with electrochemical detection was employed to measure both glutamate and GABA after derivatization with o-phthalaldehyde and sulphite in a single isocratic HPLC analysis. The non-endogenous amino acid, homoglutamine, was used as an internal standard in verifying the consistent derivatization of amino acids and in quantifying amounts of glutamate and GABA released from the caudate-putamen tissue. The derivatized amino acids (1-30 pmol) were detected as chromatographic peaks eluting at baseline level and free of significant interfering co-eluates in a 25-30 min analysis time.

Animals↗
PubMed1997

Release of endogenous glutamate and gamma-aminobutyric acid from rat striatal tissue slices measured by an improved method of high performance liquid chromatography with electrochemical detection.

The release of endogenous glutamate and gamma-aminobutyric acid (GABA) from rat brain tissue slices was studied using a tissue slice assay in which detectable amounts of the amino acids were released from 1-2 mg of tissue. An improved method of high performance liquid chromatography (HPLC) with electrochemical detection was employed to measure both glutamate and GABA after derivatization with o-phthalaldehyde and sulfide in a single isocratic HPLC analysis. The non-endogenous amino acid, homoglutamine, was used as an internal standard in verifying the consistent derivatization of amino acids and in quantifying amounts of glutamate and GABA released from the caudate-putamen tissue. The derivatized amino acids (1-30 pmol) were detected as chromatographic peaks eluting at baseline level and free of significant interfering co-eluates in a 25-30 min analysis time.

Animals↗
PubMed1997

Quantitative analysis of mu and delta opioid receptor gene expression in rat brain and peripheral ganglia using competitive polymerase chain reaction.

Competitive polymerase chain reaction assays following reverse transcription have been developed for quantitative analysis of delta and mu opioid receptor gene expression. The assay was used to obtain quantitative measurements of mu and delta opioid receptor expression levels in different brain regions and sensory and sympathetic ganglia in the rat. The assays provide accurate estimates of the relative levels of receptor messenger RNAs by the inclusion in the assays of known amounts of internal standards with the same sequence, except for a small deletion, as the target complementary DNA. The amplification products of target and competitor can be distinguished by size, and their amounts measured by densitometry. Expression of mu and delta opioid receptor messenger RNAs in different regions of the rat brain, somatic and visceral sensory and sympathetic ganglia was investigated using this method. In the brain the highest density of delta receptor messenger RNA was detected in the olfactory bulb, followed by the striatum. The mu receptor was expressed at highest levels in the midbrain-hypothalamic region. All the sensory ganglia studied expressed both mu and delta opioid receptor messenger RNAs. In the nodose ganglion we observed the highest level of mu receptor messenger RNA of any structure studied; in the trigeminal ganglion the level was about 10 times lower than that in the nodose ganglion. Among the dorsal root ganglia, mu receptor messenger RNA density was highest in the lumbar region, followed by the thoracic and cervical regions. The sympathetic superior cervical ganglion expressed a very low level of mu message. Delta receptor messenger RNA was detected only in the sensory ganglia, at levels that were considerably lower than in the striatum. The reverse transcription polymerase chain reaction assay is quantitatively reliable for comparison of messenger RNA levels between different RNA extracts, and sensitive enough to permit the detection and assay of mu and delta opioid receptor gene expression in a single pair of sensory or autonomic ganglia from the rat.

Animals↗
PubMed1997

Regulation of delta-opioid receptor mRNA levels by receptor-mediated and direct activation of the adenylyl cyclase-protein kinase A pathway.

The effects of activation of the adenylyl cyclase-protein kinase A pathway on the expression of delta-opioid receptor mRNA in the NG108-15 neuroblastoma x glioma cell line has been investigated. Activation of prostaglandin E1 (PGE1) receptors, which are positively coupled to adenylyl cyclase, resulted in a reduction in delta-receptor messenger RNA levels. Direct stimulation of adenylyl cyclase by forskolin or treatment of cells with the cyclic AMP analogue dibutyryl cyclic AMP (db-cAMP) mimicked the effect of PGE1. Down-regulation in receptor protein levels, as measured by loss of radioligand binding sites, was also observed and its extent correlated well with the decrease in the amount of delta-opioid receptor transcripts. D-Ser2-Leu-enkephalin-Thr6 (DSLET) inhibition of adenylyl cyclase activity was also diminished after db-cAMP treatment. Inhibitors of protein kinase A (PKA) partially reversed the PGE1- and db-cAMP-mediated repression of the delta-opioid receptor mRNA levels. The rate of degradation of delta-opioid receptor mRNA in the presence of actinomycin D was not altered in response to db-cAMP, suggesting that mRNA stability is not reduced by PKA action. The regulation of delta-opioid receptor mRNA levels by db-cAMP was not sensitive to the protein synthesis inhibitor cycloheximide, suggesting that de novo protein synthesis is not required in this process.

Adenylyl Cyclase Inhibitors↗
PubMed1997

The role of dopaminergic systems in opioid receptor desensitization in nucleus accumbens and caudate putamen of rat after chronic morphine treatment.

Morphine treatment of rats (60-70 mg/kg/day, 7 days) reduced delta opioid receptor-mediated inhibition of adenylyl cyclase activity in caudate putamen without any change in regulation by mu receptors. Earlier studies suggested that dopamine D1 and mu opioid receptors that regulate adenylyl cyclase are expressed preferentially by striato-nigral neurons, whereas adenosine A2a and delta1 opioid receptors are expressed preferentially by striato-pallidal neurons. Chronic morphine treatment also resulted in a reduction of dopamine D2 receptor-mediated inhibition of A2a receptor-stimulated adenylyl cyclase. Treatment with a D2 receptor antagonist (eticlopride; 1 mg/kg/day) for 7 days reduced D1 receptor stimulation of adenylyl cyclase. In contrast, chronic treatment with a D1 receptor antagonist R(+)-7-chloro-8-dihydroxy-3-methyl-1-phenyl-2,3,4, 5-tetrahydro-1H-3-benzazepine HCL (SCH 23390; 2.5 mg/kg/day) resulted in a reduction of delta1 and delta2 opioid inhibition of adenylyl cyclase, with no change in the inhibitory activity of a mu agonist. The inhibitory activity of the D2 agonist quinelorane against adenosine A2a-activated enzyme was also reduced by this treatment. Thus chronic D1 blockade, like chronic morphine treatment, appears to cause a selective impairment of the regulation of adenylyl cyclase in A2a receptor-expressing striato-pallidal neurons. D2 receptor activation appears to play an important role in the desensitization of delta receptors, because concurrent administration of the D2 antagonist eticlopride with morphine prevented the densitization of delta and D2 receptors. Similar results were obtained in nucleus accumbens, which suggests a role for D2 receptor desensitization in the adaptive response of this brain region to chronic morphine.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1996

Mu and delta opioid receptor gene expression after chronic treatment with opioid agonist.

Levels of mRNA coding for mu and delta opioid receptors were evaluated by competitive PCR in regions of rat brain where adaptive changes in opioid regulation of adenylyl cyclase occur following chronic morphine treatment. Correlation between receptor protein and mRNA levels after exposure to full and partial agonists were also investigated in NG108-15 cells. Different basal gene expression levels of mu and delta opioid receptors were found in the caudate-putamen, nucleus accumbens, thalamus and periaquaductal gray. After continuous morphine treatment for 7 days both mu and delta opioid receptor mRNA levels were unchanged in all four regions compared with saline-treated controls. In NG108-15 cells marked down-regulation of delta opioid receptors as measured by radioligand binding was observed after 5 or 24 h full agonist (D-Ser3-Leuenkephalin; DSLET) treatment. Morphine, a partial agonist at delta receptors, did not reduce receptor number at either time point. The reduction in delta receptor binding after DSLET treatment was not accompanied by significantly diminished levels of delta receptor mRNA. Unaltered mu and delta receptor mRNA levels in brain after chronic morphine exposure make it unlikely that adaptive changes in the transcription of these genes play a role in the observed tolerance in opioid regulation of adenylyl cyclase.

Animals↗
PubMed1996

Opioid regulation of intracellular free calcium in cultured mouse dorsal root ganglion neurons.

Opioid agonists induced an increase in the intracellular free calcium concentration ([Ca2+]i) or an inhibition of K+ (25 mM)-stimulated increase in [Ca2+]i in different subsets of mouse dorsal root ganglion (DRG) neurons. The total neuronal population was grouped into three classes according to somatic diameter and defined as small ( < 16 microns), intermediate (16-25 microns), or large ( > 25 microns) neurons. Substance P-like immunoreactivity was detected mainly in the small and intermediate neurons. The delta, kappa, and mu opioid receptor agonists [D-Ser2,Leu5]enkephalin-Thr (DSLET), U69593, and [D-Ala2, MePhe4, Glyol5]enkephalin (DAMGO) each induced a transient increase in [Ca2+]i in a small fraction ( < 30%) of neurons. The increases in [Ca2+]i were blocked by the opioid antagonist naloxone. The dihydropyridine-sensitive calcium channel blocker nifedipine also blocked the increase in [Ca2+]i induced by 1 microM DSLET. The rank order of potency (percentage of cells responding to each opioid agonist) was DSLET > U69593 > DAMGO. The opioid-induced increase in [Ca2+]i was observed mainly in large neurons, with a low incidence in small and intermediate neurons. Opioid agonists also caused inhibition of K(+)-stimulated increases in [Ca2+]i, which were blocked by naloxone (1 microM). Inhibition of the K(+)-stimulated increase by 1 microM DSLET or U69593 was greater in small and intermediate neurons than in large neurons.

Analgesics↗
PubMed1996

Differences among mouse strains in the regulation by mu, delta 1 and delta 2 opioid receptors of striatal adenylyl cyclases activated by dopamine D1 or adenosine A2a receptors.

It is well established that the intensity of the morphine-induced locomotor stimulatory response in rodents is genetically determined. We have evaluated the ability of mu (DAMGO). delta 1 (DPDPE) and delta 2 ([D-Ala2]deltorphin II; DT-II) selective opioid receptor agonists to inhibit receptor-activated adenylyl cyclase activity. Previous studies have shown that dopamine D1 receptors are preferentially expressed in striatonigral neurons, while adenosine A2a receptors are preferentially expressed in striatopallidal neurons. Our results indicate that in striatum of wild-type CD1 mice as in rat. mu-agonists inhibit D1-activated adenylyl cyclase, but were without inhibitory activity against A2a-activated adenylyl cyclase. In all tested mouse strains, the delta 1 selective agonist, DPDPE, inhibited the A2a-activated adenylyl cyclase but not the D1-activated enzyme. In contrast, the delta 2 agonist, DT-II, inhibited both D1 and A2a activated enzyme in all strains except DBA/2J, where DT-II did not inhibit D1-activated adenylyl cyclase. In C57BL/6J mice, which are highly sensitive to morphine-induced motor stimulation, mu agonists were potent inhibitors of A2a-activated adenylyl cyclase but did not inhibit the D1-activated enzyme, while mu opioids did not inhibit A2a-activated enzyme in DBA/2J mice which show little locomotor response to morphine. In CXBK mice, a strain with known deficiencies in mu-receptor expression, both forms of receptor-activated adenylyl cyclase were less sensitive than in CD1 mice to inhibition by DAMGO. The results suggest probable differences in the specific neural locations of opioid receptor subtypes in certain inbred strains of mice with varying sensitivities to the behavioral effects of morphine.

Adenylyl Cyclase Inhibitors↗
PubMed1996

The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter.

Meperidine has atypical opioid receptor agonist effects and shares some structural features with the phenyltropane (WIN) analogs of cocaine. In combination with 0.1 mg/kg naltrexone, meperidine produced cocaine-like discriminative stimulus effects in monkeys, whereas morphine was inactive. Both cocaine and meperidine inhibited [3H]dopamine uptake in chopped rat caudate putamen with comparable potencies; meperidine differed from cocaine in that its effects could be characterized as having predominantly a single high-affinity component. Morphine was not active in inhibiting [3H]dopamine uptake, indicating that the effect of meperidine was not via a classic mu-opioid receptor agonist action. Further, meperidine but not morphine displaced [3H]WIN 35,428 (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) binding. These data suggest that the actions of meperidine that are atypical of opioids are due to activity at the dopamine transporter. In addition, meperidine appears to interact predominantly with the high-affinity component of the dopamine transporter, and this high-affinity component may be the site of importance for the production of cocaine's behavioral effects.

Animals↗
PubMed1996

Continuous cocaine administration enhances mu- but not delta-opioid receptor-mediated inhibition of adenylyl cyclase activity in nucleus accumbens.

Cocaine alters opioid receptor densities in rat brain. To investigate the functional consequences of such opioid receptor changes, adenylyl cyclase activity was measured in rat nucleus accumbens and caudate putamen following continuous cocaine administration (50 mg/kg/day, 7 days). In the nucleus accumbens chronic cocaine led to an increase in both the number of mu-opioid receptors and the maximal inhibition of adenylyl cyclase activity by DAMGO ([D-Ala2,N-methyl-Phe4,Glyol]enkephalin). There was no effect on inhibition of adenylyl cyclase activity by DPDPE ([D-Pen2,D-Pen5]enkephalin). There were no changes in the caudate putamen. Thus, continuous cocaine administration for 7 days results in a selective increase in mu-opioid receptor-mediated effector function in the nucleus accumbens.

Adenylyl Cyclase Inhibitors↗