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Biomedical subjects

R M Kostrzewa

Publications and source records attributed to R M Kostrzewa.

At least 19 recordsLinked to original sources
PubMed1992

Supersensitized oral responses to a serotonin agonist in neonatal 6-OHDA-treated rats.

Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with supersensitization of the dopamine D1 agonist induction of oral activity. The present study was conducted to determine whether induced oral responses to serotonin (5-HT) agonists would be similarly altered in this rat model. At 3 days after birth, rats received desipramine HCl (20 mg/kg, IP) 1 h before 6-OHDA HBr (100 micrograms in each lateral ventricle) or saline-ascorbic acid (0.1%) vehicle. At approximately 9 mo, rats were challenged with the mixed 5-HT1C and 5-HT2 receptor agonist, m-chlorophenylpiperazine diHCl (m-CPP 2HCl; 0.30-6.0 mg/kg, IP) and were then observed for 1 min every 10 min over a 60-min period. m-CPP induced oral activity in both the vehicle and 6-OHDA groups, with the responses of the 6-OHDA group being much greater. An m-CPP dose of 3.0 mg/kg produced a maximal response of 63.6 +/- 3.2 oral movements in the 6-OHDA group. A bell-shaped response curve was obtained, with lower and higher doses of m-CPP producing less of an effect. Attenuation of the m-CPP-induced response by the 5-HT receptor antagonist, mianserin HCl (1.0 mg/kg, IP, 30 min before m-CPP), indicates that the m-CPP effect is receptor mediated. These findings demonstrate that neonatal 6-OHDA treatment produces ontogenic long-lived supersensitization of a 5-HT receptor system in rats.

Animals↗
PubMed1992

Effects of MPTP and vitamin E treatments on immune function in mice.

The effects of treatment with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and vitamin E, an antioxidant, on immune functions were examined. Male C57/B1 mice were fed daily with natural vitamin E for 12 weeks, subsequently injected i.p. with MPTP or its vehicle, and sacrificed 1 week later. Control mice received the stripped corn oil vehicle daily, in place of vitamin E. Oral vitamin E feeding increased cerebral vitamin E content by 60% (P = 0.05). However, MPTP attenuated this rise in cerebral vitamin E content when measured 1 week after treatment with the neurotoxin (P = 0.05). MPTP also produced an 80-90% reduction in striatal dopamine content in both the stripped corn oil control group and the vitamin E-treated group (P = 0.0000). One week after MPTP injection, the numbers of peripheral blood lymphocytes and the percent of spleen T-cells, but not B-cells, were decreased in those groups receiving MPTP alone or MPTP plus vitamin E (P less than 0.05 and 0.02, respectively). The Con A-induced IL-2 production of spleen cells was decreased in all treated groups (P less than 0.005). There was no difference in the mitogenic stimulative response to PHA, Con A or LPS. However, the response to PWM was increased in both MPTP and MPTP plus vitamin E-treated groups (P less than 0.05 and 0.001, respectively). On the other hand, the one-way mixed lymphocyte response of the splenocytes from the MPTP-treated group was increased (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Supersensitization of the oral response to SKF 38393 in neonatal 6-OHDA-lesioned rats is mediated through a serotonin system.

To study possible interactions between dopamine (DA) and serotonin (5-HT) neurochemical systems in the D-1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a series of 5-HT agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form, 1 hr) and 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). Rats were observed individually as adults, once a minute every 10 min over a 1-hr period after challenge with a DA or 5-HT receptor agonist. The respective 5-HT1A and 5-HT1B agonists, (+/-)-8-hydroxydipropylaminotetralin (0.50 mg/kg s.c.) and CGS 12066B maleate (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1, 2-alquinoxaline], 1:2 maleate salt; 3.0 mg/kg i.p.), did not increase oral activity. The mixed 5-HT1C and 5-HT2 receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a slight increase in oral activity in control rats and a marked increase in oral activity in 6-OHDA-lesioned rats. In the 6-OHDA group the peak effect of 76.5 +/- 4.1 oral movements occurred with an m-CPP 2-HCl dose of 4.0 mg/kg. Pindolol (1.0 mg/kg i.p.), ketanserin tartrate (5 mg/kg i.p.) and MDL-72222 (3-tropanyl-3,5-dichlorobenzoate; 10 mg/kg s.c.), antagonists with high affinity for 5-HT1A,1B, 5-HT2 and 5-HT3 receptors, respectively, did not attenuate m-CPP actions. However, mianserin HCl (1.0 mg/kg s.c.), an antagonist with high affinity for 5-HT1C and 5-HT2 receptors, attenuated the oral response to m-CPP.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Ontogenetic homologous sensitization to the antinociceptive action of quinpirole in rats.

Repeated postnatal treatment of rats with the dopamine receptor agonist, quinpirole results in exaggeration of selected behaviors that are induced by quinpirole in adulthood. To determine whether the antinociceptive response to quinpirole could be similarly enhanced, rats were treated daily from birth with quinpirole HCl (3.0 mg/kg per day i.p. x 28 days) and their response time in the hot plate analgesia test was determined at 4 months. An acute dose of quinpirole HCl (100 or 1000 micrograms/kg i.p.) produced an analgesic response in the neonatally primed rats and in the vehicle controls. More significantly, the effect was substantially greater in the quinpirole-primed group at each of these two doses of quinpirole. This effect of quinpirole was fully attenuated in both groups by treatment with the dopamine receptor antagonist, spiperone HCl (0.30 mg/kg i.p., 1 h before quinpirole). The analgesic effect of morphine sulfate (6.0 mg/kg i.p.) was not greater in the quinpirole-primed group. These findings demonstrate that the ontogenetic sensitization of quinpirole receptors results in enhanced antinociceptive responses to quinpirole in adulthood. This animal model may be useful for studying the involvement of dopamine systems in algesia and analgesia.

Aging↗
PubMed1991

Ontogenic homologous supersensitization of dopamine D1 receptors.

To determine whether prolonged supersensitization of dopamine D-1 receptors could be produced during ontogeny, rats were treated daily, from birth, for 33 consecutive days with the D-1 receptor agonist, SKF 38393 HCl (3.0 mg/kg per day i.p.). These rats were additionally treated at 3 days after birth with the neurotoxin, 6-hydroxydopamine HBr (6-OHDA; 200 micrograms i.c.v., half in each lateral ventricle) or its vehicle. At 6 to 7 weeks from birth a challenge dose of SKF 38393 HCl (3.0 mg/kg i.p.) increased stereotypy scores for a number of behaviors in 6-OHDA-lesioned rats that were treated repeatedly during ontogeny with SKF 38393. These accentuated behaviors included licking, grooming, taffy pulling, jumping, paw treading and locomotion. Although the findings demonstrate an increased sensitivity of D-1 receptors to an agonist, there was no change in the Bmax or Kd for D-1 receptors in the striatum. In rats that were treated during postnatal development with SKF 38393, but not lesioned with 6-OHDA, SKF 38393-induced stereotyped behaviors were not substantially different from control. The neonatally primed rat model may be useful for probing mechanisms of receptor supersensitivity.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Supersensitized D1 receptors mediate enhanced oral activity after neonatal 6-OHDA.

Enhanced oral responses have been observed in rats that are treated shortly after birth with 6-hydroxydopamine (6-OHDA). A series of studies was conducted to characterize this effect. A dose-response curve demonstrated that the dopamine D1 receptor agonist, SKF 38393, produced a maximal response in 6-OHDA-treated rats at a dose of 0.10 mg/kg (IP). With the D2 receptor antagonist, spiperone, a bell-shaped dose-response curve was seen, with a maximal effect in the 6-OHDA group occurring at 80 micrograms/kg. There were only slight increases in oral activity with different SKF 38393 or spiperone doses in the saline group, indicating that there was an overt supersensitization of D1 receptors in the 6-OHDA-treated rats. The D1 antagonist SCH 23390 (0.30 mg/kg, IP) attenuated the response to both SKF 38393 and spiperone. The oral response to the D2 agonist, quinpirole (0.10 mg/kg, IP) was not preferentially increased in the 6-OHDA group of rats. These findings indicate that the enhanced oral response in neonatal 6-OHDA-treated rats is mediated by supersensitive dopamine D1 receptors. The persistence of the enhanced oral response in 6-OHDA-treated rats at 8 months demonstrates that this sensitization of D1 receptors is a long-lived phenomenon.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Ontogenic homologous supersensitization of quinpirole-induced yawning in rats.

Yawning in male rats is a behavior that may be induced by a group of dopamine receptors when low doses of dopamine-receptor agonists are administered. To determine whether agonist treatments during postnatal development could produce a long-lived supersensitization of these dopamine receptors, rats were treated daily for the first 28 days from birth with quinpirole HCl (3.0 mg/kg/day, IP), an agonist that acts at D2 and D3 receptors. At 8 to 10 weeks from birth the dose-effect curve for quinpirole-induced yawning demonstrated that a supersensitization of dopamine receptors for yawning behavior had occurred. Yawning at the optimal dose of quinpirole HCl (100 microgram/kg, IP) was increased 2-fold. The Bmax and Kd for D2 receptor binding in rat striatum were unaltered in this group of rats. These findings indicate that dopamine receptors can be ontogenically "primed" or supersensitized, and that the phenomenon apparently is not related to changes in striatal D2 receptor binding characteristics.

Aging↗
PubMed1991

Potentiation of spiperone-induced oral activity in rats after neonatal 6-hydroxydopamine.

The influence of central dopaminergic fibers on drug-induced oral activity in rats has not been well studied. Rats were treated 3 days after birth with bilateral intracerebroventricular 6-hydroxydopamine (6-OHDA; 134 micrograms total, base form) to destroy dopaminergic fibers in the brain. Control rats received vehicle by the same route. At about 10 weeks of age, a challenge dose of the dopamine D2 receptor antagonist, spiperone (40 micrograms/kg, IP), produced an 8-fold increase in the number of oral movements during a 60-minute observation period, vs. the control group. SKF 38393 (3.0 mg/kg, IP), a D1 agonist, produced the same number of oral movements as spiperone in the 6-OHDA group, representing a 2.4-fold increase over the controls. The Bmax and Kd for both D1 and D2 receptors was not changed in rat striatum by neonatal 6-OHDA treatment, even though dopamine content was reduced by 96%. These findings demonstrate that oral activity in rats can be greatly altered, even when there is no change in absolute numbers of D1 and D2 receptors and no change in the ratio of D1:D2 receptors.

Animals↗
PubMed1991

Vitamin E supplements fail to protect mice from acute MPTP neurotoxicity.

The effect of chronic treatment with vitamin E (VE) on acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, as assessed by striatal dopamine (DA) depletion, was studied. Male C57B1/6J mice were fed VE (48 mg kg-1 per day, intragastric) for 4, 8, or 12 weeks prior to administration of MPTP (20 mg kg-1, i.p. x 3, 2 h intervals) or its diluent. Brain VE concentration was increased by exogenous supplements for 12 weeks. Striatal DA content was reduced by 85% to 90% after MPTP in control and VE-treated mice. Mice with elevated cerebral VE were not protected from MPTP toxicity, with DA content as an indicator. In conclusion, these findings indicate that moderate elevation of brain VE is not adequate for protecting DA-containing neurons against the toxic actions of a high dose of MPTP.

Animals↗
PubMed1991

Relationship between blood groups and behavior patterns in men who have had myocardial infarction.

Consistent correlations have been found between physical dysfunctional states and blood factors. Some of these disorders have possible psychosomatic components (eg, duodenal ulcer, myocardial infarction). This study focused on the relationship between blood types and various indices of behavior patterns (eg, type A behavior scores, anger ratings) in young patients who had had an initial myocardial infarction. Patients with blood type O scored significantly higher on type A behavior scales and related indices than those having blood type A. Those with blood group B responded on several scales between those with types A and O. We discuss the utility of blood groupings in future research in the prediction of myocardial infarction, methodologic limitations, the relationship of these results to temperament studies, Jenkins Activity Survey subtest patterns, anti-H reactivity pattern, and hypotheses relating blood factors and behavioral traits in patients with psychosomatic disorders.

ABO Blood-Group System↗
PubMed1989

MIF-1 attenuates apomorphine stereotypies in adult rats after neonatal 6-hydroxydopamine.

Since prolyl-leucyl-glycinamide (MIF-1) modifies the behavior of adult rats after treatment with neuroleptics, we examined whether MIF-1 would also modify adult behavior after treatment of neonatal rats with 6-hydroxydopamine (6-OHDA). Rats received 6-OHDA (100 micrograms i.c.v.) or diluent at 3 days after birth and either MIF-1 (2.0 mg/kg per day s.c. x 10 days) or diluent beginning at 28 or 29 days after birth. At 5 weeks, a low dose (0.1 mg/kg s.c.) of apomorphine increased the distance traveled, time in ambulation, number of stereotypic movements, and number of movements per time in stereotypy, but decreased the time in stereotypy in the 6-OHDA group. MIF-1 (x 7 or 8 days) showed a tendency to attenuate the increased number of movements and significantly (P less than 0.05) reduced all of the other effects of neonatal 6-OHDA. Behavior induced by higher doses of apomorphine in the 6-OHDA group (reduced licking and head nodding; increased paw treading, taffy pulling and self-biting) were not attenuated by MIF-1. At 38 or 39 days, total in vitro binding of [3H]SCH-23390 and [3H]spiroperidol to striatal homogenates was not altered in any of the groups. The findings demonstrate that specific early developmental alterations in apomorphine-induced behaviors can be modified by treatment of adult rats with MIF-1, even in the absence of overt changes in the binding of striatal dopamine D-1 and D-2 receptors.

Animals↗
PubMed1989

Impaired ontogeny of striatal dopamine D1 and D2 binding sites after postnatal treatment of rats with SCH-23390 and spiroperidol.

The effect of chronic postnatal treatment of rats with selective D1- and/or D2-receptor antagonists on the development of D1- and D2-receptors in the striatum was studied. When neonatal rats were treated postnatally from the day of birth for 32 successive days with the D1-receptor antagonist, SCH-23390 (0.30 mg/kg i.p.), the development of striatal dopamine D1-receptors was markedly impaired, and the development of striatal D2-receptors was slightly impaired. Alternatively, chronic treatment with the D2-receptor antagonist, spiroperidol (1.0 mg/kg i.p.), resulted in a markedly impaired development of striatal dopamine D2-receptors, and a slightly impaired development of striatal D1-receptors. Scatchard analysis revealed that chronic SCH-23390 treatment during development resulted in a 78% decrease in the Bmax for in vitro binding of [3H]SCH-23390 to striatal homogenates, while the Kd was unaltered. Similarly, chronic postnatal treatment with spiroperidol was associated with a 74% reduction in the Bmax, while the Kd for in vitro binding of [3H]spiroperidol to striatal homogenates was unchanged. These findings demonstrate that chronic selective dopamine receptor antagonism affects development of both striatal D1- and D2-receptor types. The critical period during which striatal dopamine receptor ontogeny can be altered is not restricted to prenatal periods, since suitable postnatal challenge will alter striatal dopamine-receptor development.

Animals↗
PubMed1989

Attenuation of SCH 23390-induced alteration of striatal dopamine D1 receptor ontogeny by prolyl-leucyl-glycinamide in the rat.

Long-term postnatal treatment of rats with SCH 23390 is associated with a reduction in the development of dopamine D1 receptors in the striatum. Because the tripeptide, L-prolyl-L-leucyl-glycinamide (PLG) attenuates the neuroleptic-induced increase in D2 receptors in the striatum in adult rats, this study was undertaken with the objective of determining whether PLG could modulate a developmental alteration in the D1 subtype of receptor. Rats were treated with the dopamine D1 receptor antagonist, SCH 23390 (R[+]-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1-H-3- benzazepine) (0.30 mg/kg/d i.p.) for 32 successive days from birth, while D1 receptors in the striatum were assessed at 5 and 8 weeks from birth. Postnatal treatment with SCH 23390 reduced in vitro binding of [3H]SCH 23390 to homogenates in the striatum by 70% at 8 weeks. Scatchard analysis at 5 weeks determined that the Bmax for the binding of [3H]SCH 23390 was reduced by 78%, while the Kd was unaltered. When PLG (1.0 mg/kg/d.i.p.) was administered together with SCH 23390 for the initial 32 days from birth, the binding of [3H]SCH 23390 to homogenates of the striatum was unchanged from that of the control group at 8 weeks. Also, at 5 weeks the Bmax and Kd were unaltered from control in the group that was treated with both SCH 23390 and PLG. The binding of [3H]SCH 23390 was not altered from control in the group treated with PLG alone. Also, PLG given in vitro did not alter the binding of [3H]SCH 23390 to control homogenates of the striatum. These findings indicate that PLG is able to attenuate neuroleptic-induced alterations in dopamine D1 receptors in the striatum.

Animals↗
PubMed1988

Impaired striatal dopamine receptor development: differential D-1 regulation in adults.

Previous reports have indicated that prenatal, but not postnatal, haloperidol impairs the ontogenic development of striatal dopamine D-2 receptors. In the present study a specific D-2 receptor antagonist, spiroperidol (1.0 mg/kg i.p.) and/or a specific D-1 receptor antagonist, SCH 23390 (0.30 mg/kg i.p.), was administered to rats for 32 successive days from birth. Postnatal spiroperidol and SCH 23390 treatments markedly impaired the development of striatal dopamine D-2 and D-1 receptors, respectively, at 12 weeks after birth. Spiroperidol did not affect D-1 receptor development and did not modify the effect of SCH 23390 treatment. Also, SCH 23390 did not affect D-2 receptor development and did not modify the effect of spiroperidol treatment. When rats with impaired development of striatal D-2 receptors were challenged at 12 weeks with spiroperidol (1.0 mg/kg per day i.p. x 17 days) D-2 receptors did not up-regulate. However, when rats with impaired development of striatal D-1 receptors were challenged at 12 weeks with SCH 23390 (0.30 mg/kg per day i.p. x 17 days) D-1 receptors did up-regulate. These findings demonstrate that postnatal treatment with D-1 and D-2 receptor antagonists can permanently impair the development of striatal D-1 and D-2 receptors. Moreover, the ability of developmentally impaired striatal D-1 receptors to up-regulate in adulthood appears to be greater than that for the developmentally impaired striatal D-2 receptors.

Animals↗
PubMed1988

Destruction of cells in the midportion of the locus coeruleus by a dorsal bundle lesion in neonatal rats.

Although insult of the developing noradrenergic neuronal system in the brain has been associated with redistribution of noradrenergic fiber input to various target brain regions, few studies have investigated the effects of such insults on locus coeruleus cell survival. In the present study the dorsal noradrenergic bundle was transected by means of a midbrain knife cut in rats 3 days after birth, and the effects of this lesion were determined approximately 8-10 weeks later. By means of an immunofluorescent histochemical procedure, it was shown that tyrosine hydroxylase-containing fibers and dopamine beta-hydroxylase-containing fibers were markedly reduced in number in the neocortex and hippocampus--regions anterograde to the site of axonal transection. It was further demonstrated that the number of fluorescent fibers coursing through the dorsal bundle was similarly reduced. Sprouting of noradrenergic fibers in the brainstem and cerebellum accompanied the above alterations. When locus coeruleus cell number was determined by counting Cresyl violet-stained nucleoli in serial sections it was found that dorsal bundle transection produced a loss of 17% of the cells of the coeruleus. By dividing the counts for each nucleus into fifths, it was additionally found that approximately 20-25% of those cells comprising the midportion of the nucleus, along a rostrocaudal axis, were the ones destroyed by axonal transection. These findings indicate that a neonatal lesion of the dorsal bundle produces a loss of cells in the midportion of the nucleus locus coeruleus, and that this effect is associated with noradrenergic neuronal hyperinnervation of the brainstem and cerebellum.

Animals↗
PubMed1986

Effects of bilateral lesion of the locus coeruleus and of neonatal administration of 6-hydroxydopamine on the concentration of individual proteins in rat brain.

The role that norepinephrine plays in regulating the concentration of different proteins in the parietal cortex, hippocampus and cerebellum was assessed by investigating the effects of either a bilateral lesion of the locus coeruleus or neonatal administration of 6-hydroxydopamine. Two weeks after lesioning the locus coeruleus, the concentration of two different proteins was elevated in the hippocampus; a third protein was reduced in concentration in this brain area as a result of the lesion. Three proteins were affected in concentration in the cerebellum after the locus coeruleus lesion--two were elevated in concentration and one was reduced in concentration. No proteins were altered in concentration in the parietal cortex as a result of the lesion. Seventy days after neonatal treatment with 6-hydroxydopamine, a total of 6 proteins were found to be changed. Four of these (one in the hippocampus and 3 in the parietal cortex) were reduced in concentration while two proteins (both in the cerebellum) were elevated in concentration after neonatal treatment with the catecholamine neurotoxin. There was little overlap between those proteins affected in concentration by the bilateral lesion of the locus coeruleus and those changed by neonatal treatment with 6-hydroxydopamine. These results suggest that the concentration of a number of different proteins may, under normal physiological conditions, be regulated in vivo by norepinephrine in the brain.

Animals↗