Biomedical subjects

D J Calcagnetti

Publications and source records attributed to D J Calcagnetti.

At least 37 records · Page 2Linked to original sources

PubMed1992

Attenuation of drinking sweetened water following calcium channel blockade.

Recent reports cite results that both cocaine-induced conditioned place preference and activity stimulation are attenuated by pretreatment with the calcium channel blocker isradipine (ISR) in rats. By blocking voltage-dependent L-type calcium channels, ISR may regulate neural dopamine release that, in turn, decreases the putative rewarding effects mediated by dopaminergic mechanisms. It is known that nonfluid deprived rats avidly consume sweetened fluids; this suggests that the sweet taste is rewarding. Three experiments were conducted to determine the effects of ISR on drinking sweetened and nonflavored water. Experiment 1 was designed to test whether ISR would attenuate the intake of a palatable solution in a dose-dependent manner. To this end, ISR was administered both peripherally (3.0-30 mg/kg) and centrally (0.3-30 micrograms/rat) prior to a solution of saccharin and d-glucose (S + G) being made available to rats (15 min/day) and intake was recorded. ISR produced dose-dependent decreases (38%-81%) in S + G intake dependent on the route of administration. In Experiment 2, water intake was measured in 18 h water-deprived rats following ISR (10 mg/kg) administration as well as comparing S + G drinking. The effect of two ISR vehicles, dimethyl sulfoxide and Tween 80, upon fluid intake was also determined. ISR injection did not attenuate water intake in 18 h water-deprived rats and the choice of vehicle did not affect the ISR-induced attenuation of S + G drinking. In Experiment 3, a single dose (30 micrograms) of ICV administered ISR, that attenuated S + G intake by approximately 44%, did not attenuate water intake in 18 h water-deprived rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Conditioned place aversion following the central administration of a novel dopamine release inhibitor CGS 10746B.

Numerous drugs of abuse that elevate brain extracellular dopamine concentrations by either increasing the firing rate of dopaminergic neurons or producing dopamine release have been shown to reliably condition a preference for place. If dopamine release is a necessary component for conditioned place preference (CPP), one reciprocal hypothesis may be that inhibition of dopamine release will result in conditioned place aversion (CPA). This hypothesis has been tested pharmacologically by employing CGS 10746B (CGS), a novel neuroleptic known to inhibit the release of dopamine via presynaptic mechanisms. In previous work the peripheral administration of CGS (1.25-20 mg/kg) produced place aversion at doses above 5 mg/kg. However, the contribution of peripheral mechanisms in the production of CGS-induced CPA is unknown. To test whether central administration of CGS would also result in CPA, rats were fitted with chronic intraventricular cannula. Groups of rats subsequently received four conditioning trials with one of four intraventricular (ICV) doses of CGS (1-30 micrograms) when confined to their preferred side of a place conditioning apparatus. Vehicle was similarly administered on four interspersed days prior to confining these same rats to their nonpreferred side of the apparatus. At the conclusion of these eight conditioning trials, the rats were tested, on separate days, in a nondrugged and a CGS-drugged state. The highest dose of CGS (30 micrograms) produced a CPA as evidenced by rats spending less time in the environment initially found to be preferred. Locomotor activity was also measured over a 30-min period with and without ICV injection of CGS (1-30 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Delta opioid antagonist, naltrindole, selectively blocks analgesia induced by DPDPE but not DAGO or morphine.

Initial reports suggest that naltrindole hydrochloride (NTI), a recently developed opioid, acts as a selective delta (delta) antagonist in vivo. Three experiments were conducted in rats to test NTI for its ability to dose-dependently and selectively block the analgesia produced by a delta-selective opioid agonist without affecting analgesia produced by mu (mu) receptor opioid agonists. Intracerebroventricular (ICV) administration of the delta-selective agonist, DPDPE (30 micrograms/rat), and the mu-selective agonist, DAGO (0.3 micrograms/rat), increased paw-lick latency (2-fold relative to baseline) in the hot-plate assay. NTI (0.01-1.0 micrograms/rat, ICV) dose-dependently attenuated DPDPE-induced analgesia (1.0 micrograms reduced paw-lick latency to baseline), but failed to affect DAGO-induced analgesia at any dose tested. A third experiment determined whether the ICV administration of NTI (1.0 micrograms/rat) would attenuate restraint stress-induced potentiation of morphine analgesia as indexed by the tail-flick assay. Rats that underwent 5 days of 1 h restraint stress and nonstressed rats were injected subcutaneously with morphine (1.0-8.0 mg/kg). The magnitude (greater than 2-fold) and duration of morphine-induced analgesia in restrained rats were significantly potentiated compared to nonstressed rats. NTI (1 microgram, ICV) failed to affect the magnitude and duration of morphine-induced analgesia regardless of restraint treatment. Thus, NTI failed to attenuate the analgesia produced by DAGO or morphine (in two assays of antinociception), whereas NTI (0.01-1.0 micrograms, ICV) antagonized dose-dependently DPDPE-induced analgesia. These results support the view that NTI is a selective delta-receptor antagonist in vivo.

Analgesia↗

PubMed1990

Factors affecting restraint stress-induced potentiation of morphine analgesia.

The analgesic effect of opioid drugs is potentiated in rats exposed to restraint stress as compared to unstressed rats. The purpose of the present study was to quantify how the following factors affect morphine-induced analgesia: habituation to restraint versus exposure to restraint for the first time, restraint stress duration, and interval from restraint to analgesic testing. Expts. 1 and 2 generated dose- and time course curves for morphine in rats exposed to one of 3 treatments: no restraint stress (NS), first exposure to 1 or 6 h of restraint (FS), or 5 days of restraint habituation followed by 1 or 6 h of restraint on the test day (HAB). Analgesia was measured by the tail-flick assay. Rats subjected to 1 h of restraint displayed dose- and time-dependent potentiation of morphine-induced antinociception compared to unstressed rats. Given 4.0 mg/kg morphine. FS-treated subjects showed 1.4- and 2.7-fold more potentiation of analgesia than HAB- and NS-treated rats, respectively. Rats restrained for 6 h prior to testing showed significant dose effect for morphine but failed to reveal significant treatment effects. Thus, increasing the duration of restraint from 1 to 6 h attenuated morphine antinociception in FS- and HAB-treated subjects to the level of NS subjects. In Expt. 3, several groups of rats underwent a single 1-h session of restraint at various time intervals prior to injection with morphine (4.0 mg/kg) and tail-flick testing. An unstressed group also receiving morphine served as control.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia↗

PubMed1990

Stress-induced tolerance to delta receptor agonist DPDPE and selectivity of the irreversible delta-ligand, DALCE.

Experiments were conducted to (1) provide further evidence of the selectivity of [D-Ala2,Leu5,Cys6]enkephalin (DALCE) as an antagonist of delta (delta) receptor ligands and (2) use DALCE as a tool to explore the possible role of delta receptors in restraint stress. Dose- and time-response curves were generated for the respective delta- and mu (mu)-selective opioid agonists DPDPE (3-30 micrograms) and DAGO (0.03-0.3 microgram) to increase the latency to paw-lick in the hot-plate test in rats. Both agonists produced robust analgesia lasting at least 20 min when injected intracerebroventricularly (i.c.v.). DALCE (0.4-10 micrograms) administered i.c.v. 24 h earlier failed to affect baseline pain sensitivity. DALCE pretreatment dose-dependently blocked the increase in paw-lick latency produced by DPDPE (30 micrograms) but not that induced by an equivalent analgesic dose of DAGO (0.3 microgram). In the last experiment we determined whether 1 h of restraint stress would (a) alter delta receptor sensitivity as indexed by DPDPE-induced analgesia and (b) attenuate the ability of DALCE to functionally antagonize DPDPE-induced analgesia. Rats were assigned to one of four treatment groups: i.c.v. vehicle injection/no stress; vehicle/stress; i.c.v. DALCE (10 micrograms)/no stress; DALCE/stress. Twenty-four hours after treatment, dose- and time-response curves were generated to test the ability of DPDPE (30-120 micrograms) to increase paw-lick latency. Prior exposure to stress alone produced tolerance to DPDPE-induced analgesia. DALCE pretreatment antagonized DPDPE similarly regardless of stress condition. The effects of both stress and DALCE were surmounted by the highest dose of DPDPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗

PubMed1990

Pharmacological profile of the potentiation of opioid analgesia by restraint stress.

Morphine-treated rats exposed to restraint stress show potentiated magnitude and duration of analgesia compared to unstressed rats. The present study was performed to assess the pharmacological characteristics of stress-induced potentiation of opioid analgesia. We tested 10 opioids to determine whether restraint stress treatment would potentiate their ability to produce antinociception indexed by the tail-flick assay. We tested full mu, delta and kappa opioid receptor agonists (fentanyl, meperidine, DPDPE, U50488H, ethylketocyclazocine), and mixed agonist/antagonists representing a range of receptor selectivities and intrinsic activities (profadol, buprenorphine, pentazocine, butorphanol and nalbuphine). Dose-effect and time-response curves were generated for unrestrained and restrained rats after either subcutaneous (SC) and/or intracerebroventricular (ICV) injections. In restrained rats, all drugs except for SC-administered nalbuphine produced dose- and time-dependent analgesic effects of greater magnitude (1.5-3 times) than they produced in unrestrained rats. However, restrained rats given agonists with high intrinsic activity at the mu receptor displayed the most potent and consistent potentiation of analgesia compared to unrestrained controls. Our results suggest that activation of the mu receptor is of primary importance for restraint to potentiate analgesia, because restrained rats injected with delta and kappa agonists displayed potentiation of analgesia only at doses high enough to possibly exceed the selective activation of their respective receptor types.

Animals↗

PubMed1990

Centrally administered opioid antagonists, nor-binaltorphimine, 16-methyl cyprenorphine and MR2266, suppress intake of a sweet solution.

Three opioid antagonists (MR2266, 16-methyl cyprenorphine and nor-binaltorphimine) were tested independently for their ability to suppress the intake of a highly palatable saccharin and glucose (S/G) solution after central administration. MR2266 is an equally potent antagonist at kappa (kappa) and mu (mu) opioid receptors. Nor-binaltorphimine (N-BNI) and 16-methyl cyprenorphine (M80) are two recently developed opioid antagonists that were chosen based upon their ability to act more selectively than naloxone at kappa and delta (delta) opioid receptor types, respectively. Prior research has demonstrated that when dissolved in acid and administered centrally, MR2266 (20 micrograms) fails to suppress S/G intake. Because all three antagonists are rather insoluble in water, they were dissolved in dimethyl sulfoxide (DMSO). Rats with chronic ventricular cannula were allowed to consume S/G for a 0.5 hr bout. They received a single intracerebroventricular (ICV) injection of antagonist (MR2266: 0, 10, 20 and 40 micrograms; M80: 0, 5, 10, 20 and 40 micrograms or N-BNI: 0, 1, 3, and 10 micrograms) 10 min prior to the start of the drinking bout. Administration of DMSO alone failed to alter drinking relative to saline, whereas each antagonist significantly attenuated S/G intake. We conclude that, when dissolved in DMSO, these antagonists suppress drinking by blockade of opioid receptors.

Animals↗

PubMed1989

Delta opioid antagonist, 16-Me cyprenorphine, selectively attenuates conditional fear- and DPDPE-induced analgesia on the formalin test.

The effects of 16-Me cyprenorphine (M80) on the antinociception produced by reexposing rats to a chamber associated with footshock (1 mA, 0.75 sec) 24 hr earlier was assessed with the formalin test. In Experiment 1, intracerebroventricular administration of M80 dose-dependently (0.5-8 micrograms) reversed conditional analgesia. Experiment 2 demonstrated that M80 (5 micrograms) had no effect on baseline pain sensitivity, but completely reversed conditional analgesia. Experiment 3 demonstrated that 0.25 micrograms DAGO, 3.5 micrograms DPDPE, and 28 micrograms U50,488H all produced equivalent levels of antinociception on the formalin test. The 5 micrograms dose of M80 completely reversed the antinociception produced by DPDPE but did not influence that produced by DAGO or U50,488H. These data suggest, that at the doses employed, M80 is a selective delta-opioid receptor antagonist and that delta-receptors are involved in conditional fear-induced analgesia.

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

PubMed1989

Suppression of juvenile social behavior requires antagonism of central opioid systems.

Pairs of male and female rats were injected with either tertiary naltrexone (NTX) which readily crosses the blood-brain barrier, or quaternary naltrexone (QNTX) which does not, to determine the importance of central opioid systems in the elaboration of juvenile social behavior. In the first experiment, only intraperitoneal injections of NTX (1.0 mg/kg) suppressed the frequency of wrestling pins. Peripheral injections of QNTX (10.0 mg/kg) were without effect. In a second experiment, QNTX (2.0, 4.0, or 8.0 micrograms/4.0 microliters) was injected directly into the lateral ventricles. Intracerebroventricular injection of the moderate dose reliably reduced frequency of pinning while the higher dose was severely incapacitating and the low dose was without effect. The results of these two experiments confirm an important role for brain opioid systems in the control of juvenile social interaction.

Animals↗

PubMed1989

Modulation of appetitively and aversively motivated behavior by the kappa opioid antagonist MR2266.

MR2266 (MR), an opioid antagonist that binds to kappa and mu receptors, was examined for its ability to influence the aversively motivated behaviors conditioned by electric shock and the drinking induced by water deprivation or the availability of a palatable saccharin/glucose solution. The intraperitoneal (ip) and intracerebroventricular (icv) administration routes were contrasted. After both ip and icv administration, MR was able to reverse conditional analgesia as measured by the formalin test. MR enhanced the Pavlovian conditional freezing response when administered icv prior to shock exposure but reduced freezing if given ip prior to shock. A related benzomorphan-derived opioid antagonist, MR1452, also reduced freezing when given ip prior to shock. MR2266 was a potent antidipsogenic agent when administered ip but had no such effect when administered icv. It is concluded that separable opioid systems are involved in the modulation of appetitively and aversively motivated behaviors.

Animals↗

PubMed1989

Role of mu and kappa opioid receptors in conditional fear-induced analgesia: the antagonistic actions of nor-binaltorphimine and the cyclic somatostatin octapeptide, Cys2Tyr3Orn5Pen7-amide.

When rats are returned to an environment in which they previously received electric shock they show a reduction in sensitivity to painful stimuli. This conditional fear-induced analgesia was measured using the formalin test. The octapeptide Cys2Tyr3Orn5Pen7-amide (CTOP; 0, 10, 40 and 160 ng/rat) dose-dependently reversed conditional analgesia when administered i.c.v. The 40-ng dose partially attenuated fear-induced analgesia, whereas the 160-ng dose reversed it completely. Using similar procedures, CTOP was tested for its ability to reverse the analgesia produced by i.c.v. administered [D-Ala2,-NMPhe4, Glyol5]-enkephalin, [D-Pen2,D-Pen5]-enkephalin and U50488H, which are highly selective opioid agonists at mu, delta and kappa receptors, respectively. At 40 ng/rat, CTOP reversed the analgesia produced by the mu selective ligand but not that produced by the delta ligand or the kappa ligand. At 80 ng CTOP antagonized the analgesia produced both by both enkephalin analogs but not U50488H. Nor-binaltorphimine (0, 1, 3, 10 and 30 micrograms/rat) had no effect on conditional analgesia. However, the 10- and 30-micrograms doses could reverse completely the analgesia produced by U50488H. Therefore, it appears that mu and delta, but not kappa receptors, are involved in this opioid form of stress-induced analgesia.

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

PubMed1988

Analgesia produced by centrally administered DAGO, DPDPE and U50488H in the formalin test.

Three opioid agonists ([D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAGO), [D-Pen2,D-Pen5]enkephalin (DPDPE) and U50488H) were tested independently for their ability to produce analgesia in the formalin test. These agonists were chosen based upon their ability to act selectively at mu, delta and kappa opioid receptor types respectively. Rats received one intracerebroventricular (i.c.v.) injection of an agonist 20 min after subcutaneous injection of 15% formalin into a rear paw. Formalin injection produces continuous pain that results in two stereotypic behaviors, paw licking and paw lifting. Ten minutes after i.c.v. injection rats were observed for an 8 min period and scored for formalin-induced behavior. All agonists produced analgesia as indicated by a dose-dependent attenuation of formalin-induced behavior. At the doses tested, the rank order of analgesic efficacy was DAGO greater than DPDPE greater than U50488H. We suggest that centrally located mu, delta and kappa opioid receptors can each modulate the perception of this clinically relevant form of continuous pain. Additionally, the highest dose of DPDPE tested significantly increased rearing whereas DAGO and U50488H failed to affect rearing.

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

PubMed1988

Peripheral versus intracerebroventricular administration of quaternary naltrexone and the enhancement of Pavlovian conditioning.

When rats are placed in a context with mild electric shock (1 mA/0.75 s), the environmental cues alone can provoke an immobile crouching behavior termed freezing. Freezing response is a Pavlovian conditional response provoked by stimuli that come to be associated with shock. Previous research has shown that peripheral injection of opioid antagonists can enhance this response. Two experiments were conducted to determine if peripheral and/or central opioid mechanisms are involved in this enhancement of freezing by employing quaternary naltrexone (QNTX), an opioid antagonist which does not readily penetrate the 'blood-brain barrier'. QNTX (5 and 10 micrograms/rat) administered i.c.v. prior to shock significantly enhanced freezing 24 h later, whereas i.p. injected QNTX, at doses as high as 20 mg/kg, had no effect. These results suggest that the enhancement of conditional freezing produced by QNTX is mediated by central, not peripheral, opioid mechanisms.

Animals↗

PubMed1988

Ethylketocyclazocine and bremazocine analgesia in neonatal rats.

In three experiments we examined the analgesic potency of kappa opioid receptor agonists in 2- and 16-day-old rats. Ethylketocyclazocine (1-50 mg/kg) produced similar dose- and time-dependent increases in the latency to retract a hind paw from a noxious thermal stimulus in rats of both ages. Bremazocine (0.001-10 mg/kg), a kappa agonist with reported antagonist activity at mu receptors, was also effective in producing analgesia in 2-day-old rats. The dose-effect relationship for bremazocine was nonmonotonic. Bremazocine analgesia (0.1 mg/kg) was reversed by both naltrexone and MR2266, a putative kappa opioid antagonist. These results are discussed in terms of the functional integrity of a kappa analgesic system in the developing rat.

Analgesia↗

PubMed1987

Central and peripheral injection of quaternary antagonist, SR58002C, reduces drinking.

Earlier research has demonstrated that opioid involvement in drinking is primarily mediated centrally [8,10]. Drinking is attenuated by the centrally and peripherally active opioid antagonists naloxone and naltrexone in doses as low as 1.0 mg/kg, but not by the quaternary forms of these antagonists [4]. Peripherally administered quaternary forms of these antagonists fail to suppress drinking in doses as high as 10 mg/kg. We generated dose-response curves for centrally and peripherally administered SR58002C, a "newer" quaternary opioid antagonist purported to have high peripheral selectivity, on drinking in 23.5 hr water deprived rats. SR58002C was administered both intracerebroventricularly (ICV, 0, 10, 40 and 80 micrograms/rat) and intraperitoneally (IP, 0, 10, 40 and 80 mg/kg). Doses of SR58002C above 10 mg/kg IP or 10 micrograms ICV significantly reduced drinking in comparison to controls. However, SR58002C appears to be less potent than quaternary naltrexone in suppressing drinking after ICV administration.

Animals↗

PubMed1987

Quaternary naltrexone reveals the central mediation of conditional opioid analgesia.

Earlier research has demonstrated that when rats are placed in a context associated with mild electric shock (1 mA/0.75 sec), environmental cues alone can produce conditional analgesia that suppresses pain sensitivity on the formalin test. This analgesia appears to be mediated by endogenous opioids since it is reversed by the centrally active opioid antagonists naloxone and naltrexone. Two experiments attempted to determine if peripheral or central opioids mediate this analgesia by employing quaternary naltrexone (QNTX), an antagonist which does not readily penetrate the blood-brain barrier at moderate doses. Intracerebroventricularly administered QNTX (10 micrograms) significantly reversed conditional analgesia, whereas intraperitoneally injected QNTX did not affect formalin-induced behavior. These results suggest that the conditional analgesia produced by our procedures is mediated by central, not peripheral, opioid mechanism(s).

Animals↗

PubMed1987

Opioid-induced linear running in obese (ob/ob) and lean mice.

Earlier research has shown that opioids stimulate behavioral activation in mice whereas opioid antagonists attenuate this activation. We conducted an experiment to determine the dose-response curve of FK33824, a potent Met-enkephalin analogue. FK33824 produced an unusual form of behavioral activation we called "linear running" in which the mice ran continuously in one direction and were nearly oblivious to environmental stimuli. This may be the kind of running that occurs naturally during migration. Wheel running activity of genetically obese (ob/ob) and lean (C57BL/6J ?/+) mice was measured following the intracerebroventricular infusion of 0.1, 1.0, 10.0 and 100.0 ng of FK33824. The lowest dose did not alter baseline running, whereas the 1.0 and 10.0 ng doses significantly increased running in both genotypes. We found a genotype difference with the highest dose tested, the lean mice ran at baseline levles and displayed ataxia whereas the obese mice continued to show increased running without ataxia. We hypothesize that genetic differences in the enkephalin mechanisms of C57 lean and obese mice are responsible for linear running.

Animals↗

PubMed1983

Morphine and acceptability of putative reinforcers.

Rats were given the opportunity to take one of five concentrations of saccharin solutions. Intake across concentrations generated a preference-aversion curve. Morphine, 2 mg/kg, increased intake of saccharin solutions when rats were 12-hr water deprived or were not deprived. These effects with morphine are opposite to those of naloxone and strengthen the idea that there is opioid involvement in incentive motivation.

Aging↗