Biomedical subjects

L F Tseng

Publications and source records attributed to L F Tseng.

At least 73 records · Page 4Linked to original sources

PubMed1996

Pretreatment with pertussis toxin differentially modulates morphine- and beta-endorphin-induced antinociception in the mouse.

The experiments were designed to determine the role of pertussis toxin-(PTX) sensitive G-proteins Gi/Go in the brain and spinal cord in antinociception induced by epsilon-opioid receptor agonist beta-endorphin (beta-EP) and mu-opioid receptor agonist morphine. The effects of intracerebroventricular (i.c.v.) or intrathecal (i.t.) pretreatment with PTX on antinociception induced by morphine, beta-endorphin (beta-EP) and other selective opioid receptor agonists given i.c.v. or i.t. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. An i.c.v. pretreatment with PTX (0.5 microgram) caused a time- and dose-dependent attenuation of the tail-flick and hot-plate inhibition induced by i.c.v.-challenged morphine-induced antinociception. However, the same pretreatment with PTX did not affect the antinociception induced by i.c.v.-administered beta-EP. The tail-flick and hot-plate inhibition induced by selective mu-, delta- and kappa-opioid receptor agonist, DAMGO, [D-Ala2]deltorphin II and U50,488H, respectively, given i.c.v. was also attenuated by the i.c.v. pretreatment with PTX. An i.t. pretreatment with PTX (0.5 microgram) blocked markedly the tail-flick inhibition induced by morphine and beta-EP given i.c.v. However, the same treatment did not affect the hot-plate inhibition induced by beta-EP and attenuated, to a lesser degree, the hot-plate inhibition induced by morphine given i.c.v. An i.t. pretreatment with PTX blocked the tail-flick inhibition induced by selective delta 2-, alpha 2 and 5-HT receptor agonist [D-Ala2]deltorphin, norepinephrine and 5-HT, respectively, given i.t. Our results indicate that the antinociception induced by mu-, delta-, kappa-opioid receptor agonists given supraspinally is mediated by respectively opioid receptors that are coupled to PTX-sensitive Gi/Go proteins at the supraspinal sites and subsequently mediated by the activation of PTX-sensitive Gi/Go coupled receptors in the spinal cord. However, the antinociception induced by beta-EP given supraspinally is mediated by the PTX-resistant epsilon-opioid receptors at the supraspinal sites and subsequently activation of the delta 2-opioid receptors in the spinal cord that is sensitive to the pretreatment with PTX.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1995

Pretreatment with pertussis toxin blocks morphine- but not beta-endorphin-induced antinociception in the mouse.

We have previously demonstrated that the antinociception induced by morphine and beta-endorphin given intracerebroventricularly (i.c.v.) is mediated by the stimulation of respective mu- and epsilon-opioid receptors. The effects of i.c.v. pretreatment with pertussis toxin on the antinociception induced by morphine and beta-endorphin given i.c.v. were studied in male ICR mice. Antinociception was assessed by the tail-flick and hot-plate tests. Pretreatment with pertussis toxin (0.5 microgram) given i.c.v. 96 h earlier blocks the antinociception induced by i.c.v. administered morphine in both tail-flick and hot-plate tests. The same pretreatment did not affect the antinociception induced by i.c.v. administered beta-endorphin. Our results indicate that morphine-, but not beta-endorphin-induced antinociception is mediated by pertussis toxin sensitive G-proteins.

Analgesics, Opioid↗

PubMed1995

Pretreatment with beta-endorphin facilitates the attenuation of delta-opioid receptor-mediated antinociception caused by delta-opioid receptor antisense oligodeoxynucleotide.

Intracerebroventricular (i.c.v.) pretreatment of male ICR mice with beta-endorphin (0.6 nmol) or intrathecal (i.t.) pretreatment with antisense oligodeoxynucleotide to delta-opioid receptor mRNA (163 pmol) alone given 24 h earlier did not have any effect on i.t. administered delta-opioid receptor agonist [D-Ala2]deltorphin II (6.4 nmol)-induced antinociception. However, a concomitant i.c.v. pretreatments with beta-endorphin (0.08-0.6 nmol) and i.t. pretreatment with delta-opioid receptor antisense oligodeoxynucleotide (163 pmol) for 24 h dose-dependently attenuated i.t. challenged [D-Ala2]deltorphin II-induced antinociception. A concomitant i.c.v. pretreatment with mu-opioid receptor agonist [D-Ala2,N MePhe4,Gly(ol)5]enkephalin (DAMGO) or kappa-opioid receptor agonist U50,488H and i.t. pretreatment with delta-opioid receptor antisense oligodeoxynucleotide for 24 h did not affect i.t. challenged [D-Ala2]deltorphin II-induced antinociception. beta-Endorphin given supraspinally has been documented to release [Met5]enkephalin acting on delta-opioid receptors in the spinal cord. Our results indicate that supraspinal pretreatment with beta-endorphin selectively causes a loss of spinal delta-opioid receptor-mediated antinociception in mice receiving delta-opioid receptor antisense oligodeoxynucleotide.

Animals↗

PubMed1995

Antisense oligodeoxynucleotide to a delta-opioid receptor blocks the antinociception induced by cold water swimming.

The type of opioid receptors in the spinal cord involved in antinociception induced by cold water swimming (CWS) was studied in male ICR mice. Mice were submitted to CWS for 3 min and antinociception was measured 7 min after the CWS by the tail-flick test. Intrathecal (i.t.) injection of naltrindole (NTI, 5 micrograms) which blocked i.t. DPDPE ([D-Pen2,D-Pen5]en-kephalin, 5 micrograms)-induced antinociception, blocked the CWS-induced antinociception. On the other hand, i.t. injection of CTOP (D-Phe-Cys-Try-D-Try-Orn-Thr-Pen-Thr-NH2, 50 ng) and norbinaltorphimine (nor-BNI, 5 micrograms) which blocked i.t. DAMGO ([D-Ala2,NHPhe4,Gly-ol]enkephalin, 10 ng)- and U50,488H (trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide, 75 micrograms)-induced antinociception, respectively, did not block CWS-induced antinociception. Intrathecal pretreatment with antisense oligodeoxynucleotide to delta-opioid receptor mRNA (delta-AS oligo, 163 pmol) once a day for 1 to 3 days caused a time-dependent attenuation of CWS-induced antinociception. delta-AS at doses from 1.6 to 163 pmol pretreated i.t. for 3 days caused a dose-dependent blockade of CWS-induced antinociception. However, i.t. pretreatment with mismatch oligodeoxynucleotide (MM oligo, 163 pmol) for 3 days did not affect the CWS-induced antinociception. The results indicate that CWS-induced antinociception is mediated by the stimulation of delta-opioid receptors in the spinal cord.

Amino Acid Sequence↗

PubMed1995

Stimulation of spinal delta-opioid receptors in mice selectively enhances the attenuation of delta-opioid receptor-mediated antinociception by antisense oligodeoxynucleotide.

Intrathecal (i.t.) pretreatment of male ICR mice with antisense oligodeoxynucleotide to delta-opioid receptor mRNA once a day for 1-3 days caused a time-dependent attenuation of i.t. administered [D-Ala2]deltorphin II-induced antinociception as measured by the tail-flick test. The attenuation of the antinociception induced by i.t. administered [D-Ala2]deltorphin II, a delta-opioid receptor agonist, was enhanced by i.t. pretreatment for 1 day with [D-Ala2]deltorphin II, but not [D-Ala2,N MePhe4,Gly(ol)5]enkephalin (DAMGO), a mu-opioid receptor agonist, or U50,488H, a kappa-opioid receptor agonist, given together with antisense oligodeoxynucleotide to delta-opioid receptor mRNA. The present results indicate that stimulation of spinal delta-opioid receptors by i.t. injection of [D-Ala2]deltorphin II selectively causes a loss of delta-opioid receptor-mediated antinociception in mice pretreated with antisense oligodeoxynucleotide to delta-opioid receptor mRNA.

Analgesics↗

PubMed1995

Inhibition of protein kinase C, but not of protein kinase A, blocks the development of acute antinociceptive tolerance to an intrathecally administered mu-opioid receptor agonist in the mouse.

A specific protein kinase C inhibitor, calphostin C, which injected alone had no effect on the antinociception induced by intrathecal (i.t.) administration of a selective mu-opioid receptor agonist, [D-Ala2,NMePhe4,Gly(ol)5]enkephalin (DAMGO), dose-dependently attenuated the development of acute tolerance to the i.t. DAMGO-induced antinociception in male ICR mice. On the other hand, a selective protein kinase A inhibitor, KT5720, did not have any effect on the development of acute tolerance to DAMGO antinociception. These findings suggest that protein kinase C, but not protein kinase A, plays an important role in the development of acute tolerance to the mu-opioid receptor agonist-induced antinociception.

Analgesics↗

PubMed1995

Spinal delta 2-, but not delta 1-, mu-, or kappa-opioid receptors are involved in the tail-flick inhibition induced by beta-endorphin from nucleus raphe obscurus in the pentobarbital-anesthetized rat.

The antinociception induced by beta-endorphin given supraspinally has been previously demonstrated to be mediated by the release of [Met5]enkephalin acting on delta-opioid receptors in the spinal cord. The present study was designed to determine what type of opioid receptors in the spinal cord is involved in beta-endorphin-induced antinociception in the rat. Antinociception was induced by beta-endorphin (0.6 nmol) given into nucleus raphe obscurus and was assessed by the tail-flick test in pentobarbital-anesthesized rats. Naltriben (0.6-6.0 nmol), a selective delta 2-opioid receptor antagonist, given intrathecally dose-dependently attenuated beta-endorphin-induced inhibition of the tail-flick response. On the other hand, 7-benzylidene naltrexone (2.1-64.3 nmol), CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, 0.09-2.8 nmol), or nor-binaltorphimine (1.4-40.8 nmol), selective delta 1-, mu-, and kappa-opioid receptor antagonists, respectively, did not block beta-endorphin-induced antinociception. The results of present study in rats are consistent with previous experiments in mice indicating that spinal delta 2-, but not delta 1-, mu- or kappa-opioid receptors are involved in beta-endorphin-induced inhibition of the tail-flick response.

Amino Acid Sequence↗

PubMed1995

Differential ontogenesis of thermal and mechanical antinociception induced by morphine and beta-endorphin.

The antinociceptive effects induced by beta-endorphin and morphine given supraspinally have been previously demonstrated to be mediated by the activation of different neural mechanisms. The present experiments were to examine the effects of intraventricular administration of beta-endorphin and morphine in mechanical paw-withdrawal and thermal tail-flick nociceptive tests in rats of 2-28 days of age. 2-4-day-old neonates were not responsive to i.c.v. injection of beta-endorphin or morphine for the inhibition of the tail-flick response. The thermal antinociceptive responses induced by beta-endorphin and morphine started to develop in 7-14-day-old rats and continued to increase at 21-28 days. The inhibition of the mechanical paw-withdrawal response to beta-endorphin was already present in 2-day-old rats and morphine in 4-day-old rats. The mechanical antinociception progressively increased and reached a plateau at 7 days of age for beta-endorphin and 28 days of age for morphine. beta-Endorphin was found to be more efficacious than morphine in producing mechanical antinociception. The results demonstrate that beta-endorphin- and morphine-induced antinociception to mechanical and thermal stimuli develops differently and are consistent with the hypothesis that two descending pain inhibitory systems activated by beta-endorphin and morphine are differentially developed.

Aging↗

PubMed1995

The antinociception induced by beta-endorphin administered intrathecally is mediated by the activation of mu- and kappa-opioid receptors in the rat.

The antinociception induced by beta-endorphin given supraspinally has been previously demonstrated to be mediated by the stimulation of epsilon-, but not mu-, delta- or kappa-opioid receptors in rats and mice. The present study was designed to determine what types of opioid receptors in the spinal cord are involved in the antinociception induced by intrathecally (i.t.) administered beta-endorphin. Antinociception was assessed by the tail-flick test in male Sprague-Dawley rats. CTOP (0.9-6.6 nmol), a selective mu-opioid receptor antagonist, or nor-BNI(13.6-95.3 nmol), a selective kappa-opioid receptor antagonist, given i.t. dose-dependently reversed i.t. administered beta-endorphin-induced inhibition of the tail-flick response. On the other hand, naltrindole (6.6-44.4 nmol), a selective delta-opioid receptor antagonist, or beta-endorphin (1-27) (1-6.7 nmol), a selective epsilon-opioid receptor antagonist given i.t., did not antagonize the inhibition of the tail-flick response induced by i.t. administered beta-endorphin. The results are consistent with the previous study in mice [Tseng LF and Collins KA (1992) Eur J Pharmacol 214: 59-65] that the antinociception induced by beta-endorphin given i.t. is mediated by the stimulation of mu- and kappa-, but not delta- and epsilon-opioid receptors.

Animals↗

PubMed1995

Differential modulation by muscimol and baclofen on antinociception induced by morphine, beta-endorphin, D-Pen2,5-enkephalin and U50,488H administered intracerebroventricularly in the mouse.

The present study was designed to investigate the modulatory effects of stimulation of GABAA and GABAB receptors at supraspinal sites on antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. The effects of the GABAA and GABAB receptor agonists, muscimol and baclofen respectively, on the antinociception induced by morphine (a mu-receptor agonist), beta-endorphin (an epsilon-receptor agonist), D-Pen2,5-enkephalin (DPDPE, a delta-receptor agonist) and U50,488H ([trans-3,4-dichloroN-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeocetamide]; a kappa-receptor agonist) injected intracerebroventricularly (i.c.v.) were studied. The antinociception was assayed using the tail-flick and hot-plate tests. Muscimol at doses of 25-200 ng, administered i.c.v. alone did not affect the latencies of tail-flick and hot-plate thresholds, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by i.c.v. administered morphine (2 micrograms), beta-endorphin (1 microgram), DPDPE (10 micrograms), and U50,488H (60 micrograms). Baclofen (1.25-10 ng) administered i.c.v. alone did not affect the latencies of the tail-flick and hot-plate responses, but attenuated dose-dependently the inhibition of the tail-flick and hot-plate responses induced by beta-endorphin and U50,488H, without affecting morphine- or DPDPE-induced responses. Our results indicate that activation of GABAA receptors at the supraspinal sites by i.c.v. injection of muscimol antagonizes antinociception induced by supraspinally administered mu-, epsilon-, delta-, and kappa-opioid receptor agonists. On the other hand, activation of GABAB receptors at supraspinal sites by i.c.v. baclofen antagonizes antinociception induced by i.c.v. administered epsilon- and kappa-opioid agonists, but not mu- or delta-opioid agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1995

Non-NMDA receptor antagonist attenuates antinociception induced by morphine but not beta-endorphin, D-Pen2-D-Pen5-enkephalin, and U50, 488H administered intracerebroventricularly in mice.

The antinociception induced by morphine but not beta-endorphin, D-Pen2-D-Pen5-enkephalin (DPDPE), or U50, 488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) cyclohexyl] benzeocetamide) administered intracerebroventricularly (i.c.v.) has been previously demonstrated to be mediated by the N-Methyl-D-Aspartic Acid (NMDA) receptor. The present study was designed to determine if non-NMDA receptors are involved in opioid-induced antinociception. Antinociception was assessed by the tail-flick test in male ICR mice. Various doses of CNQX (6-Cyano-7-nitroquinoxaline-2,3-dione), a competitive non-NMDA receptor antagonist, (0.001 to 0.5 microgram) injected intracerebroventricularly (i.c.v.) alone did not show any antinociceptive effect. CNQX (0.01 to 1 micrograms, i.c.v.) dose-dependently attenuated the inhibition of the tail-flick response induced by morphine (1 microgram). However, inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin (1 microgram), DPDPE (10 micrograms), or U50, 488H was not affected by i.c.v. administered CNQX. It is concluded that non-NMDA receptors are involved in i.c.v. morphine-induced antinociception. However, non-NMDA receptors are not involved in i.c.v. administered beta-endorphin-, DPDPE-, and U50, 488H-induced antinociception at the supraspinal level.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Nitric oxide/cyclic guanosine monophosphate system in the spinal cord differentially modulates intracerebroventricularly administered morphine- and beta-endorphin-induced antinociception in the mouse.

Our study was designed to study the modulatory role of nitric oxide/cyclic guanosine monophosphate in the spinal cord on the antinociception induced by morphine and beta-endorphin given supraspinally. The antinociception was assessed by the tail-flick test in male ICR mice. The antinociception induced by intracerebroventricularly (i.c.v.) administered morphine was potentiated by intrathecal (i.t) injection of N omega-nitro-L-arginine (2 micrograms), hemoglobin (120 micrograms) or methylene blue (5 micrograms), but was attenuated by i.t. administered L-arginine (20 micrograms) or 3-morpholino-sydnonimine (SIN-1, 5 micrograms). In contrast, the antinociception induced by i.c.v. administered beta-endorphin was attenuated by i.t. pretreatment with N omega-nitro-L-arginine (2 micrograms) and the attenuation of beta-endorphin-induced antinociception by N omega-nitro-L-arginine was reversed by i.t. administered L-arginine (20 micrograms). The antinociception induced by i.c.v. administered beta-endorphin was also attenuated by i.t. administration of hemoglobin (120 micrograms) or methylene blue (5 micrograms). Intrathecal pretreatment with L-arginine did not affect i.c.v. administered beta-endorphin-induced antinociception. It is concluded that the inhibition of nitric oxide/cyclic guanosine monophosphate system in the spinal cord potentiates i.c.v. administered morphine-induced antinociception but attenuates i.c.v. beta-endorphin-induced antinociception. The activation of nitric oxide/cyclic guanosine monophosphate system in the spinal cord attenuates i.c.v. administered morphine-induced antinociception but does not affect i.c.v. administered beta-endorphin-induced antinociception.

Analgesics↗

PubMed1994

Differential antagonism by MK-801 against antinociception induced by opioid receptor agonists administered supraspinally in mice.

Various doses of MK-801 ((+/-)-5-methyl-10,11-dihydro-5H-dibenzo(a,d) cyclohepten-5, 10-imine maleate), a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist (0.001-1 microgram) injected intracerebroventricularly (i.c.v.) alone did not show any antinociceptive effect. MK-801 (0.001-1 microgram i.c.v.) dose dependently attenuated the inhibition of the tail-flick and hot plate responses induced by i.c.v. administered morphine (1 microgram), [D-Pen2, D-Pen5]enkephalin (DPDPE; 10 micrograms), and U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeoce tamide ) 60 micrograms). However, the inhibition of the tail-flick and hot plate responses induced by i.c.v. administered beta-endorphin (1 microgram) was not changed by i.c.v. administered MK-801. Our results indicate that, at the supraspinal level, NMDA receptors are involved in the production of antinociception induced by supraspinally administered morphine, DPDPE, and U50,488H but not beta-endorphin.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1994

Role of nitric oxide/cyclic GMP in i.c.v. administered beta-endorphin- and (+)-cis-dioxolane-induced antinociception in the mouse.

(+)-cis-Dioxolane (0.5-2 micrograms), a muscarinic receptor agonist, given intracerebroventricularly (i.c.v.) produced a dose-dependent inhibition of the tail-flick response in male ICR mice. (+)-cis-Dioxolane given i.c.v. at a subanalgesic dose (0.25 micrograms), selectively potentiated the antinociceptive response induced by i.c.v. administered beta-endorphin, an epsilon-opioid receptor agonist, but not morphine or [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO), mu-opioid receptor agonists, [D-Pen2,D-Pen5]enkephalin (DPDPE), a delta receptor agonist, or trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methane sulfonate (U50,488H), a kappa-opioid receptor agonist. The antinociceptive response induced by (+)-cis-dioxolane given i.c.v. was attenuated by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). The antinociception induced by carbachol given i.c.v. was also antagonized by the i.c.v. treatment with N omega-nitro-L-arginine (1 microgram). However, the same treatment with N omega-nitro-L-arginine, hemoglobin or methylene blue did not affect the beta-endorphin-induced antinociception. The potentiation of beta-endorphin-induced antinociception by (+)-cis-dioxolane was reversed by i.c.v. treatment with N omega-nitro-L-arginine (1 microgram), hemoglobin (120 micrograms) or methylene blue (10 micrograms). On the other hand, the antinociceptive response induced by (+)-cis-dioxolane (1 microgram) given i.c.v. was potentiated by i.c.v. administered L-arginine (20 micrograms) but not D-arginine (20 micrograms). Dibutyryl cyclic GMP at 0.5-2.0 micrograms given i.c.v. produced an antinociceptive response and at subanalgesic dose (0.1 microgram) potentiated i.c.v. beta-endorphin-induced antinociception.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1994

Antisense oligodeoxynucleotide to a delta-opioid receptor selectively blocks the spinal antinociception induced by delta-, but not mu- or kappa-opioid receptor agonists in the mouse.

An antisense oligodeoxynucleotide (A-oligo) to delta-opioid receptor mRNA was utilized to block the expression of mouse delta-opioid receptor in the spinal cord of male ICR mice. Intrathecal treatment with A-oligo (1.6-163 pmol) dose-dependently attenuated the antinociception induced by i.t. administered DPDPE ([D-Pen2,5]enkephalin) or [D-Ala2]deltorphin II, delta-opioid receptor agonist, without affecting the antinociception induced by DAMGO ([D-Ala2-MePhe4,Gly(ol)5]enkephalin) or U50,488H, respective mu- or kappa-opioid receptor agonists. Scrambled sense oligodeoxynucleotide (163 pmol) was ineffective against the tail-flick inhibition induced by DPDPE,[D-Ala2]deltorphin, DAMGO or U50,488H. The studies confirm previous pharmacological studies at the molecular level indicating a distinct delta-opioid receptor for antinociception in the spinal cord.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1994

Antisense oligodeoxynucleotide to a delta-opioid receptor given intrathecally blocks i.c.v. administered beta-endorphin-induced antinociception in the mouse.

The antinociception induced by supraspinally administered beta-endorphin is mediated by the release of Met-enkephalin and subsequent stimulation of delta-opioid receptors from the spinal cord in mice. Repeated intrathecal administration of an antisense oligodeoxynucleotide against delta-opioid receptors selectively attenuated i.c.v. administered beta-endorphin-induced antinociception without any effect on the antinociception induced by mu-opioid receptor agonists, morphine and DAMGO, or kappa-opioid receptor agonists, U50,488H. A random sequence oligodeoxynucleotide was inactive against beta-endorphin-induced antinociception. The study confirms previous findings that the antinociception induced by beta-endorphin is mediated by the stimulation of the delta-opioid receptors in the spinal cord.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1994

The effects of protection by D-Pen2-D-Pen5-enkephalin or D-Ala2-NMePhe4-Gly-ol-enkephalin against beta-chlornaltrexamine in the spinal cord on the antinociception induced by beta-endorphin administered intracerebroventricularly in the mouse.

Chlornaltrexamine (beta-CNA, 0.5 micrograms) alone or beta-CNA plus either mu-agonist, D-Ala2-NMePhe4-Gly-ol-enkephalin (DAMGO, 500 ng) or delta-agonist, D-Pen2-D-Pen5-enkephalin (DPDPE, 10 micrograms) was injected intrathecally (i.t.) to protect mu- or delta-opioid receptors, respectively, for 24 h in male ICR mice. The antinociception was assessed by the tail-flick and hot-plate test. DPDPE or DAMGO injected i.t. increased inhibition of the tail-flick and hot-plate response in a dose-dependent manner. The dose-response curve for tail-flick and hot-plate response induced by DPDPE or DAMGO in i.t. saline-treated group significantly shifted to the right in i.t. beta-CNA alone treated group but returned to the control level in the group treated with i.t. beta-CNA coadministered with DPDPE or DAMGO, respectively. The effects of protection of mu- and delta-opioid receptor in the spinal cord on inhibition of the tail-flick and hot-plate response induced by beta-endorphin and morphine administered intracerebroventricularly (i.c.v.) were then studied. Intrathecal pretreatment with beta-CNA or beta-CNA coadministered with DAMGO attenuated inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. However, i.t. treatment with beta-CNA coadministered with DPDPE did not affect inhibition of the tail-flick response induced by beta-endorphin administered i.c.v. Intrathecal pretreatment with beta-CNA or beta-CNA coadministered with either DPDPE or DAMGO did not alter inhibition of the hot-plate response induced by beta-endorphin administered i.c.v.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

Partial antinociceptive cross-tolerance to intracerebroventricular beta-endorphin in mice tolerant to systemic morphine.

The effects of subcutaneous morphine pellet-implantation on antinociception induced by intracerebroventricular (i.c.v.) administration of beta-endorphin or morphine and intrathecal (i.t.) administration of morphine, [D-Pen2,D-Pen5]enkephalin (DPDPE), [D-Ala2,NMePhe4,Gly5-ol]enkephalin (DAMGO), serotonin or norepinephrine were studied in male ICR mice. The tail-flick and hot-plate responses were used for antinociceptive tests. The ED50 values for i.c.v. administered morphine for antinociception in morphine pellet-implanted mice were increased from 3.3- and 2.2-fold at 0 h to 14.2- and 19.0-fold at 4 h and declined to 4.8- and 3.0-fold at 8 h after pellet removal in the tail-flick and hot-plate tests, respectively. On the other hand, the ED50 values for i.c.v. administered beta-endorphin for antinociception were only slightly increased (1.7- to 5.1-fold increases) throughout the same time course. The inhibition of the tail-flick response induced by i.t. injection of morphine, DPDPE and serotonin, but not norepinephrine or DAMGO, was attenuated in morphine pellet-implanted mice. These findings are consistent with previous studies indicating that different neuronal mechanisms are involved in morphine- and beta-endorphin-induced antinociception.

Analgesics↗