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A A Larson

Publications and source records attributed to A A Larson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Antinociception induced by 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1- phosphonic acid (CPP), an N-methyl-D-aspartate (NMDA) competitive antagonist, plus 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA antagonist, differs from that induced by MK-801 plus DNQX.

Excitatory amino acid receptors have been implicated in mediating pain. 3-((+-)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) antagonist and MK-801, a phencyclidine (PCP) ligand and non-competitive NMDA antagonist, were injected intrathecally in mice alone or in combination with 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA antagonist. When tested in the formalin model of pain, antinociception following CPP plus DNQX was greater than that after MK-801 plus DNQX in both the acute and tonic phases. These dissimilarities are not consistent with activity of CPP and MK-801 at the same sites in the spinal cord.

Animals↗
PubMed1994

Substance P analogs displace sigma binding differentially in the brain and spinal cord of the adult mouse.

We have previously observed similarities in the behavioral effects produced by the NH2-terminus of the undecapeptide substance P (SP) and by 1,3-di(2-tolyl)-guanidine (DTG) in the adult mouse. The present series of experiments indicate differences in the rank-order of potency of sigma ligands [DTG; haloperidol (HAL)], SP analogs [SP; SP(1-7); SP(5-11); [D-Pro2, D-Phe7]-SP(1-7) (D-SP(1-7))] and miscellaneous compounds [morphine (MOR), naloxone (NAL)] at competing for [3H]-DTG binding sites in the mouse brain and spinal cord in vitro: Brain; DTG = HAL >> SP = MOR = NAL >> SP(1-7) >> D-SP(1-7) >> SP(5-11): Spinal cord; DTG = HAL >> SP(1-7) = MOR = NAL >> SP >> D-SP(1-7) = SP(5-11). The observed difference in the rank-order potencies of the displacing ligands at these same binding sites supports the notion of two distinct populations of sigma binding sites in these tissues in the adult mouse. Given the low (micromolar) potency of SP analogs at displacing [3H]-DTG binding in the present series of experiments, it is unlikely that the similar behavioral effects we have previously observed elicited by SP(1-7) and DTG in the adult mouse are a result of a direct action of SP(1-7) at the sigma binding site.

Animals↗
PubMed1994

Activity at phencyclidine and mu opioid sites mediates the hyperalgesic and antinociceptive properties of the N-terminus of substance P in a model of visceral pain.

Substance P, a putative neurotransmitter or neuromodulator of nociception or pain in the spinal cord, exhibits both antinociceptive and hyperalgesic properties. Investigators have shown that the N-terminal metabolite of substance P, substance P(1-7), produces naloxone-reversible antinociception when given supraspinally and systemically in mice and hyperalgesia when injected intrathecally in rats. The goal of our investigation was to identify the receptors mediating these actions of substance P(1-7) at the initial site of release of substance P, i.e. in the spinal cord. Thirty minutes after intrathecal injection, substance P(1-7) produced naloxone-reversible antinociception in a dose-dependent manner in the abdominal stretch assay. When administered with naloxone, substance P(1-7) produced hyperalgesia 5 and 10 min after injection, which was inhibited by dizocilpine (MK-801), a phencyclidine ligand and non-competitive antagonist of N-methyl-D-aspartate. Antinociception was inhibited by the mu-selective opioid antagonist beta-funaltrexamine, but not by the mu 1-selective opioid antagonist naloxonazine or the delta-selective antagonist naltrindole, indicating a mu 2-opioid receptor-mediated effect. These findings suggest that the N-terminal portion of substance P may modulate nociception or pain, as demonstrated in the acetic acid abdominal stretch (writhing) assay, via activation of two different receptor systems. Substance P(1-7)-induced hyperalgesia is mediated by a phencyclidine-sensitive mechanism and antinociception involves activity at mu-opioid, most likely mu 2, receptors.

Animals↗
PubMed1994

Density of NMDA-coupled and uncoupled 1-[1-(2-[3H]thienyl) cyclohexyl]piperidine recognition sites in the brain and spinal cord: differential effects of NMDA agonists and antagonists.

Binding of 1-[1-(2-[3H]thienyl)cyclohexyl]piperidine ([3H]TCP) to mouse brain and spinal cord membranes was studied using compounds selective for the NMDA-coupled 1-(1-phenylcyclohexyl)piperidine (PCP) and/or sigma recognition sites. In both tissues, [3H]TCP labeled two populations of binding sites. Density of the low-affinity sites was approximately the same in both tissues, but the population of the high-affinity [3H]TCP sites was three times bigger in the brain than in the spinal cord. Self- and cross-displacement studies showed that the high-affinity [3H]TCP binding sites could be identical with NMDA receptor-coupled PCP sites, whereas the low-affinity [3H]TCP sites may be associated with sigma binding sites in both tissues. The NMDA-coupled PCP sites labeled in the presence of 6.25 nM [3H]TCP constituted a much higher percentage of the total binding in the brain (75%) than in the spinal cord (44%). Consistent with this, reintroduction of glycine and glutamate significantly increased, but DA antagonists significantly inhibited [3H]TCP binding in the brain but not in the spinal cord. Together, these data suggest that a large component of [3H]TCP-labeled binding sites in the spinal cord may be associated with sigma but not the NMDA receptor-coupled PCP sites.

Animals↗
PubMed1994

Adenosine receptors are not involved in theophylline-induced seizures.

One of the most dangerous aspects of theophylline toxicity is seizures. A review of the literature suggests that current anticonvulsant therapy remains far from optimal. As it is known that some of the pharmacologic effects of theophylline occur via antagonism of the adenosine A1 receptor, we tested the hypothesis that agonists acting at the adenosine A1 receptor can inhibit seizures caused by toxic doses of theophylline in mice. Dose-response curves were constructed for the ability of theophylline to produce tonic seizures in animals pre-treated with vehicle or several adenosine A1 receptor agonists. The LD50 (95% CI) for each dose-response curve was calculated. The results of these experiments showed that pretreatment with the direct-acting adenosine A1 agonists carbamazepine and cyclohexyladenosine and the indirect-acting agonist dipyridamole each failed to inhibit the ability of theophylline to cause tonic seizures (p > 0.05). Failure of these drugs to protect against theophylline-induced seizures suggests these seizures are produced by other mechanisms. Based on our results, adenosine A1 agonists, such as carbamazepine, appear to offer no therapeutic benefit in the treatment of theophylline-induced seizures.

Adenosine↗
PubMed1994

Role of the NH2-terminus of substance P in the inhibition by capsaicin of behavioral sensitization to kainic acid-induced activity in the adult mouse.

Activation of primary afferent C-fibers by repeated intrathecal injection of kainic acid (KA) in mice is inhibited after pretreatment with capsaicin. The increased behavioral response to multiple injections of KA is thought to be brought about by an action of the NH2-terminus of substance P (SP). In light of our recent observation that the antinociceptive effect of capsaicin may also involve an action of the NH2-terminus of SP, we tested the hypothesis that capsaicin inhibits behavioral sensitization to KA by a desensitization to the action of the NH2-terminus of SP. Using adult mice, pretreatment (24 hr) with either capsaicin (0.8 micrograms) or SP(1-7) (1 and 10 nmol) attenuated sensitization of the behavioral response to four injections of 25 pmol of KA at 2-min intervals. Pretreatment with 10 nmol of the COOH-terminal SP fragment, SP(5-11), had no effect. [D-Pro2,D-Phe7]-SP(1-7), a SP NH2-terminal antagonist, injected 5 min before capsaicin or SP(1-7), inhibited the effects of both capsaicin and SP(1-7) on KA sensitization whereas the COOH-terminal neurokinin antagonist, [D-Pro2,D-Trp7,9]-SP, did not. The similarities in behavioral responses after treatment with SP(1-7) or capsaicin, together with the sensitivity of these effects to D-SP(1-7), suggest that SP released in response to capsaicin may inhibit subsequent KA-induced activity 24 hr later. This action of SP appears to be brought about by its NH2-terminus and/or an accumulation of its NH2-terminal metabolites after capsaicin treatment.

Amides↗
PubMed1994

An antinociceptive effect of capsaicin in the adult mouse mediated by the NH2-terminus of substance P.

Capsaicin in the adult animal is believed to evoke a massive release of substance P (SP) and a subsequent loss of primary afferent C-fiber activity. Given the antinociceptive effect of SP N-terminal metabolites, the present experiments were designed to compare behavioral and nociceptive responses after treatments with capsaicin or the SP NH2-terminal fragment, SP(1-7), and to determine whether they share a common mechanism of action. When adult mice were tested using the hot-plate assay, 24 hr after intrathecal injections of either capsaicin (0.3-2.6 nmol) or SP(1-7) (22.5 pmol-10 nmol), a dose-related antinociception was observed. The caudally directed biting and scratching behaviors induced by 1 nmol of capsaicin injected intrathecally were also greatly reduced 24 hr after either 2.6 nmol of capsaicin or 10 nmol of SP(1-7). Pretreatment with an antagonist of the NH2-terminus of SP, [D-Pro2,D-Phe7]-SP(1-7), prevented the long-term effects of capsaicin and of SP(1-7) on capsaicin-induced behaviors in our paradigm at doses that the COOH-terminal antagonist of neurokinin activity, [D-Pro2,D-Trp7,9]-SP, did not. The antinociceptive effect of capsaicin in the adult animal is, therefore, mimicked by SP(1-7) and attenuated by [D-Pro2,D-Phe7]-SP(1-7), suggesting that the NH2-terminus of SP and its NH2-terminal metabolites, released in response to capsaicin, may contribute to the mediation of capsaicin's antinociceptive effect.

Analgesics↗
PubMed1994

The NH2-terminus of substance P modulates NMDA-induced activity in the mouse spinal cord.

Excitatory amino acids (EAAs) and substance P are believed to transmit nociceptive information in the spinal cord. As substance P NH2-terminal fragments can modulate non-NMDA EAA-mediated activity, we examined the effects of substance P fragments to ascertain whether the COOH- or NH2-terminus of substance P modulates the actions of NMDA in the spinal cord. NMDA activity was measured by the intensity of behaviors produced by NMDA (0.2 nmol) administered intrathecally in the mouse. The NMDA response was attenuated after pretreatment with either substance P (22.5 pmol, 30 min) or the NH2-terminal fragment of substance P, SP-(1-7). Pretreatment with the COOH-terminal fragment SP-(5-11) (22.5 pmol, 30 min), a neurokinin ligand, had no effect on NMDA-induced behaviors, suggesting that the inhibitory effect of substance P is caused by the NH2-terminus. Pretreatment with D-Pro2,D-Phe7 substance P-(1-7), a SP-(1-7) antagonist, potentiated NMDA activity, suggesting a tonic inhibitory effect of the substance P NH2-terminus. Desensitization to NMDA typically develops when NMDA is injected at 2 min intervals. While pretreatment with SP-(1-7) inhibited NMDA, coadministration of SP-(1-7) (22.5 pmol), with the first of four injections of NMDA, first inhibited but then potentiated responses to each challenge with NMDA. Coadministration of the same dose of SP-(1-7) with the fourth injection of NMDA immediately potentiated the response to NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Substance P N-terminal metabolites and nitric oxide mediate capsaicin-induced antinociception in the adult mouse.

The present investigation describes the antinociceptive effect of capsaicin in the acetic acid-induced abdominal stretch assay and its mediation by substance P(1-7) fragment [SP(1-7)] and nitric oxide (NO). When injected intrathecally 24 hr before testing, SP(1-7) produced a dose-related decrease in the number of abdominal stretches induced by an i.p. injection of acetic acid. The antinociceptive effect of SP(1-7) (10 nmol) persisted for 62 hr after its injection, a time course that was similar to that produced by a dose of capsaicin (2.6 nmol) that produced an effect of similar magnitude. Antinociception induced by 10 nmol of SP(1-7) was completely reversed by coadministration of 10 nmol of D-SP(1-7); the equivalent antinociception produced by capsaicin was reversed by as small a dose as 1 nmol of D-SP(1-7). The guanylate cyclase inhibitor, methylene blue, at a dose of 10 nmol, prevented both SP(1-7)- and capsaicin-induced antinociception. Capsaicin-induced, but not SP(1-7)-induced, antinociception was prevented by Nw-nitro-L-arginine methyl ester, an NO synthase inhibitor. This inhibition of capsaicin was reversed by coadministration of 120 nmol of L-arginine. Reduced hemoglobin did not prevent capsaicin-induced antinociception. These findings suggest NO is produced and acts within capsaicin-sensitive primary afferent fibers in the dorsal spinal cord to mobilize substance P, resulting in N-terminal induced-antinociception.

Analgesia↗
PubMed1994

Involvement of NMDA receptors in naloxone-induced contractions of the isolated guinea pig ileum after preincubation with morphine.

N-Methyl-D-aspartate (NMDA) antagonists attenuate morphine tolerance and dependence. To test the hypothesis that morphine increases NMDA activity, generating conditions necessary for withdrawal, we examined the role of NMDA receptors in the action of morphine in the guinea pig ileum (GPI). Glutamate produced contractions of the GPI with an EC50 of 24.6 microM. Morphine inhibited contractions induced by glutamate (10-500 microM) with a Ke of 10.2 nM. Naloxone, which produced no effect alone, prevented the inhibitory effects of morphine on glutamate-induced contractions (Ke = 19.3 nM) as well as on electrically induced contractions (Ke = 18.0 nM), suggesting that opioid receptors with similar affinities mediate both inhibitory effects of morphine. Exposure to morphine for 10 to 50 min resulted in acute dependence, characterized by contractions induced by 0.1 to 4 microM naloxone. Responses to naloxone were maximal after a 20-min incubation with 50 nM morphine. Increasing the concentration of morphine or the incubation time did not further increase the degree of dependence. Competitive ((+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) and R(-)-2 amino-5-phosphonovaleric acid) and noncompetitive (MK-801) antagonists of NMDA inhibited naloxone-induced contractions. After 20 min of incubation with morphine followed by naloxone challenge, the EC50 for glutamate was decreased by a factor of 3.2, reflecting an enhanced sensitivity to NMDA. These data show that activation of NMDA receptors and enhanced sensitivity to glutamate are important components of naloxone-precipitated contractions of the GPI after incubation with morphine.

Animals↗
PubMed1993

Possible role of the N-terminus of substance P in kainic acid-induced toxicity in rats.

Subcutaneously administered kainic acid (KA) in the rat results in brain damage accompanied by a behavioral response characterized by wet dog shakes (WDS), seizures and brain damage, an effect that is potentiated by opioids. Based on the potentiative effect of the N-terminus of substance P (SP) on the ability of KA to induce behavioral responses in mice, we tested the hypothesis that the N-terminus of SP also plays a role in KA-induced neurotoxicity in rats. Pretreatment i.p. with 1 or 10 nmol of SP(1-7), a major N-terminal metabolite of the undecapeptide SP, 15 min before administration of 12 mg/kg of KA potentiated the incidence of WDS. In contrast, after administration of 1 nmol of [D-Pro2, D-Phe7]SP(1-7) (D-SP(1-7)), the D-isomer of SP(1-7) and a substance P N-terminal antagonist, the intensity of KA-induced WDS was no different from those in either the KA- or saline-injected rats. However, pretreatment with D-SP(1-7) completely blocked the potentiative effect of SP(1-7) on the KA-induced WDS. While the severity of KA-induced lesions was not significantly altered by pretreatment with 1 nmol of SP(1-7), the effect of KA was not significantly different from that in control rats when administered with 1 nmol of D-SP(1-7). These results suggest a possible involvement of endogenous SP N-terminal activity in the effects following subcutaneous (s.c.) administration of KA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

MK-801 inhibits the effects of capsaicin in the adult mouse by an action involving phencyclidine (PCP) sites not linked to NMDA activity.

Capsaicin in the adult animal causes antinociception due to the massive release of neurotransmitters, including substance P (SP), from primary afferent C-fibers. The results of the present study indicate that capsaicin-induced antinociception in the adult is sensitive to inhibition by dizocilpine (MK-801). The failure of a high dose (10 nmoles) of (+-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) to mimic the effect of MK-801 (1 nmole) on antinociception induced by 0.8 micrograms of capsaicin suggests that the inhibition by MK-801 is mediated by a phencyclidine (PCP) site but is not associated with NMDA activity. The inability of haloperidol (1 nmole) to affect the actions of capsaicin argues against an interaction with sigma sites. Behavioral sensitization to intrathecally administered kainic acid (KA) has been proposed to reflect similar neuronal activity to that underlying pain transmission. KA sensitization is inhibited by pretreatment with capsaicin (0.8 microgram) or SP(1-7) (10 nmoles) and the influence of MK-801, CPP and haloperidol on these inhibitory effects of capsaicin and SP(1-7) were identical to those on capsaicin-induced antinociception. These data are consistent with the hypothesis that the antinociceptive effect of capsaicin in the adult is similar to that of the N-terminus of SP, both of which involve a pathway sensitive to MK-801 but not mediated by NMDA-type activity.

Animals↗
PubMed1993

Substance P-(1-7), a substance P metabolite, inhibits withdrawal jumping in morphine-dependent mice.

Substance P has been previously shown to inhibit the intensity of the morphine abstinence syndrome in mice. In view of the rapid degradation of substance P after its release from nerve terminals, we hypothesized that this inhibition is mediated by the N-terminus of substance P and its metabolites rather than via the C-terminus interacting with neurokinin receptors. Intrathecal injection of substance P-(1-7) (1 nmol) 30 min prior to naloxone challenge, in mice that had received 25 micrograms of morphine sulfate intrathecally once daily for three days, caused a dose-related attenuation of withdrawal jumping. In contrast, administration of the substance P-(1-7) antagonist, [D-Pro2,D-Phe7]substance P-(1-7), 15 min prior to naloxone increased withdrawal jumping behaviors. Equimolar doses of morphine and naloxone at 30 min had no effect. From these data, it appears that substance P N-terminal metabolites modulate withdrawal behaviors in morphine-dependent mice.

Animals↗
PubMed1993

Capsaicin inhibits whereas rhizotomy potentiates substance P-induced release of excitatory amino acids in the rat spinal cord in vivo.

The origin of the excitatory amino acids (EAA) aspartate (Asp) and glutamate (Glu) released into the dorsal spinal cord extracellular fluid of rats following intradialysate infusion of substance P (SP) was studied using neonatal capsaicin, dorsal rhizotomy and proximal spinal cord transection. Neonatal capsaicin (50 mg/kg i.p.) had no effect on basal EAA release, but significantly inhibited SP-induced release of both Asp (86%) and Glu (70%). Bilateral dorsal rhizotomy enhanced SP-induced release of Asp (152%) and had no effect on Glu release compared to sham-operated controls. Proximal spinal transection (T8-9) had no effect on basal or SP-induced release of EAAs compared to sham-operated controls. The ability of neonatal capsaicin to inhibit, and dorsal rhizotomy to potentiate Asp release correlates well with their distinct effects on hyperalgesia and suggests that these manipulations do not produce identical lesions. Neonatal capsaicin likely interferes with the normal development of EAA interneurons innervated by SP primary afferent C-fibers. Rhizotomy may result in a compensatory up-regulation of SP receptors on EAA interneurons.

Animals↗
PubMed1993

Regulation of sigma activity by the amino-terminus of substance P in the mouse spinal cord: involvement of phencyclidine (PCP) sites not linked to N-methyl-D-aspartate (NMDA) activity.

Behavioral responses to kainic acid (KA) injected intrathecally in mice are enhanced by N-but not C-terminal fragments of substance P (SP). Repeated injections of KA result in sensitization to KA-induced activity, an effect that appears to be mediated by SP N-terminal activity and inhibited by PCP ligands. The present study was initiated to determine whether the ability of SP N-terminal fragments to enhance KA activity is also sensitive to PCP ligands. We compared the effect of a PCP ligand, dizocilpine (MK-801), to that of haloperidol, a sigma ligand and dopamine antagonist. MK-801 (1 nmol) failed to alter the enhancement of behavioral responses to KA (25 pmol) produced by SP(1-7) (22.5 pmol, 30 min). However, pretreatment with 1 nmol of either haloperidol or the N-terminal SP antagonist, [D-Pro2-D-Phe7]SP(1-7) [D-SP(1-7)], prevented potentiation of KA by SP(1-7). Like SP(1-7), 5 nmol of the sigma ligand 1,3-di(2-tolyl)guanidine (DTG) also enhanced behaviors elicited by KA, and this effect was also blocked by haloperidol or D-SP(1-7), but not spiperone (2.5 nmol), a dopamine antagonist. Together these data suggest that sigma receptors are involved in the potentiation of KA. A large dose of SP(1-7) (10 nmol) or DTG (20 nmol) did not alter the response to KA 24 hr later, yet further potentiated responses to KA 30 min after SP(1-7) (22.5 pmol) or DTG (5 nmol), suggesting sensitization to the effects of these compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

MK-801 and phencyclidine act at phencyclidine sites that are not linked to N-methyl-D-aspartate activity to inhibit behavioral sensitization to kainate.

Sensitization to the behavioral effects of intrathecal kainate in mice depends on an accumulation of the N-terminus of substance P in the spinal cord and may reflect similar synaptic activity as that underlying pain transmission. The purpose of this study was to determine whether kainate sensitization, like pain, is sensitive to inhibition by phencyclidine ligands. Doses that selectively inhibit the behavioral response to a single injection of N-methyl-D-aspartate, but not kainate, were established for two non-competitive antagonists, dizocilpine (MK-801) and phencyclidine, as well as two competitive antagonists, D-amino-5-phosphonovaleric acid and (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, of N-methyl-D-aspartate. Using these doses, we found that 1 nmol of MK-801 or 3 nmol of phencyclidine blocked sensitization to four injections of 25 pmol of kainate administered at 2 min intervals. In contrast, 1.48 nmol of D-amino-5-phosphonovaleric acid and 0.5 nmol of (+/-)-3)2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid failed to alter sensitization to kainate, indicating that activation of N-methyl-D-aspartate receptors is not necessary for kainate sensitization. Haloperidol (1 nmol), a sigma receptor ligand, also failed to inhibit sensitization to kainate, suggesting that the actions of MK-801 and phencyclidine were not produced by a non-selective effect at sigma sites. Together, these data suggest that MK-801 and phencyclidine inhibit behavioral sensitization to kainate via phencyclidine receptors that are not linked to the N-methyl-D-aspartate receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

Modulation of kainic acid-induced activity in the mouse spinal cord by the amino terminus of substance P: sensitivity to opioid antagonists.

Behavioral sensitization to kainic acid (KA) in the mouse spinal cord appears to be mediated by the amino (N) terminus of substance P (SP), as potentiation of KA is sensitive to capsaicin, mimicked by SP1-7 but not SP5-11, and blocked by SP1-7 antagonists but not by neurokinin antagonists. As naloxone inhibits some effects of SP1-7, this study examines the role of opioid receptors in the mediation of KA-induced sensitization by the N terminus of SP. All drugs were injected i.t. Behavioral sensitization to repeated injections of KA was inhibited by a large (1 micrograms) dose of naloxone. Pretreatment with either naloxonazine or beta-funaltrexamine, mu-selective opioid antagonists, naltrindole, a delta-selective opioid antagonist, or nor-binaltorphimine, a kappa-selective antagonist, failed to alter the development of sensitization to KA, indicating that this phenomenon is not due to mu, delta, or kappa opioid receptors. The ability of 22.5 pmol of SP1-7 to enhance subsequent KA responses was blocked when coadministered with 0.1 micrograms of naloxone. When administered with KA, naloxone not only failed to reverse the potentiative effect of SP1-7, but further enhanced responses to KA for 2 hr after SP1-7. In contrast to pretreatment with SP1-7, coadministration of KA with SP1-7 inhibited the intensity of behaviors. The inhibitory effect of SP1-7 on responses to a single injection of KA was prevented by pretreatment with naltrindole, whereas pretreatment with beta-funaltrexamine blocked the inhibitory effect of SP1-7 on response to KA in a KA-sensitized animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗