Biomedical subjects

Richard J Bodnar

Publications and source records attributed to Richard J Bodnar.

32 records · Page 2Linked to original sources

PubMed2003

Dopamine D1 and D2 antagonists reduce the acquisition and expression of flavor-preferences conditioned by fructose in rats.

The effects of dopamine (DA) D(1) and D(2) receptor antagonists on the acquisition and expression of flavor-preferences conditioned by the sweet taste of fructose were examined. Food-restricted rats were trained over eight alternating one-bottle sessions to drink an 8% fructose solution containing one novel flavor (CS+) and a less preferred 0.2% saccharin solution containing a different flavor (CS-). Three groups of rats were treated daily with either vehicle (control group), SCH23390 (200 nmol/kg; D(1) group), or raclopride (200 nmol/kg; D(2) group) during training. Additional groups of vehicle-treated rats had their daily training intakes matched to that of the D(1) and D(2) groups. Preferences were assessed in two-bottle tests with the CS+ and CS- flavors presented in 0.2% saccharin solutions following doses of 0, 50, 200, 400, or 800 nmol/kg of either D(1) or D(2) antagonists. The D(1) and D(2) groups, unlike the control and yoked-control groups, failed to display a significant CS+ preference in the two-bottle tests following vehicle treatment. In addition, treatment with SCH23390 prior to the two-bottle tests blocked the expression of the CS+ preference in the control groups. Pretest raclopride treatment attenuated the CS+ preference at some dose levels. Raclopride also attenuated the preference for fructose in rats given two-bottle training with the CS+/fructose (CS+/F) and CS-/saccharin (CS-/S) solutions. These findings indicate that D(1) and D(2) antagonists block flavor-preference conditioning by sweet taste and that D(1), and to a lesser extent D(2), receptor antagonists attenuate the expression of a previously acquired preference.

Animals↗

PubMed2003

Differential dose-dependent effects of central morphine treatment upon food intake in male and female rats receiving neonatal hormone manipulations.

Male rats display significantly greater analgesic responses following morphine than female rats, with neonatal gonadal manipulations reversing the sex-dependent pattern. The present study assessed whether dose-dependent (0.0005-5 microg, icv) effects of morphine-induced feeding were sensitive to sex-dependent and neonatal gonadectomy manipulations. Sex differences in morphine-induced feeding varied as a function of morphine dose with males showing greater increases at low (0.0005 microg) doses, and females showing greater increases at high (5 microg) doses. Neonatal castration, respectively, enhanced and reduced morphine-induced feeding at very low (0.0005 microg) and low (0.005 microg) doses. In contrast, neonatal testosterone administered to females enhanced morphine-induced feeding at higher (0.5-5 microg) doses. These data indicate that sex and neonatal gonadectomy differences in morphine-induced feeding are dependent upon the dose of morphine employed.

Analgesics, Opioid↗

PubMed2002

Feeding induced by food deprivation is differentially reduced by G-protein alpha-subunit antisense probes in rats.

Antisense oligodeoxynucleotide (AS ODN) probes directed against the alpha-subunit of different G-proteins have been used to differentiate feeding responses in rats elicited by different opioid agonists, including morphine, beta-endorphin and dynorphin. Furthermore, antisense probes directed against G(o)alpha, but not G(s)alpha, G(q)alpha or G(i)alpha, significantly reduced nocturnal feeding in rats. The present study examined whether food intake and weight changes elicited by 24 h of food deprivation were significantly altered by ventricular administration of antisense probes directed against either G(i)alpha(1), G(i)alpha(2), G(i)alpha(3), G(s)alpha, G(o)alpha, G(q)alpha or G(x/z)alpha as well as a control nonsense probe in rats. Deprivation-induced weight loss was significantly enhanced by antisense probes directed against G(s)alpha and G(x/z)alpha, whereas weight recovery 24 h following reintroduction of food was significantly reduced by antisense probes directed against G(i)alpha(2), G(q)alpha and G(o)alpha. Selective antisense probe effects were noted for deprivation-induced intake with G(s)alpha and G(q)alpha probes exerting the greatest reductions, G(x/z)alpha, G(i)alpha(2), and G(i)alpha(3) probes exerting lesser effects, and G(i)alpha(1) and G(o)alpha probes failing to affect deprivation-induced intake. Importantly, the nonsense control probe failed to alter deprivation-induced intake or weight. The reductions in deprivation-induced intake by AS ODN probes directed against G(s)alpha or G(q)alpha were not accompanied by any evidence of a conditioned taste aversion. These data indicate important distinctions between G-protein mediation of different effector signaling pathways mediating feeding responses elicited under natural (e.g. nocturnal feeding) and regulatory challenge (e.g. food deprivation) conditions.

Animals↗

PubMed2002

Regulation of glycoprotein Ib-IX-von Willebrand factor interaction by cAMP-dependent protein kinase-mediated phosphorylation at Ser 166 of glycoprotein Ib(beta).

The platelet receptor for von Willebrand factor (VWF), glycoprotein (GP) Ib-IX, mediates initial platelet adhesion and activation. It is known that the cytoplasmic domain of GPIbbeta is phosphorylated at Ser(166) by cAMP-dependent protein kinase (PKA). To understand the physiological role of GPIbbeta phosphorylation, a GPIb-IX mutant replacing Ser(166) of GPIbbeta with alanine (S166A) and a deletion mutant lacking residues 166-181 of GPIbbeta (Delta165) were constructed. These mutants, expressed in Chinese hamster ovary (CHO) cells, showed an enhanced VWF-binding function compared with wild type GPIb-IX. Treatment of CHO cells expressing wild type GPIb-IX with a PKA inhibitor, PKI, reduced Ser(166) phosphorylation and also enhanced VWF binding to GPIb-IX. Furthermore, cells expressing S166A or Delta165 mutants showed a significantly enhanced adhesion to immobilized VWF under flow conditions. Consistent with the studies in CHO cells, treatment of platelets with PKI enhanced VWF binding to platelets. In contrast, a PKA stimulator, forskolin, reduced VWF binding and VWF-induced platelet agglutination, which was reversed by PKI. Thus, PKA-mediated phosphorylation of GPIbbeta at Ser(166) negatively regulates VWF binding to GPIb-IX and is one of the mechanisms by which PKA mediates platelet inhibition.

Amino Acid Sequence↗

PubMed2002

Alterations in food intake elicited by GABA and opioid agonists and antagonists administered into the ventral tegmental area region of rats.

Food intake is significantly increased following administration of mu-selective opioid agonists into the ventral tegmental area (VTA) region acting through multiple local opioid receptor subtypes. Since GABA receptor agonists in the VTA region are capable of eliciting feeding, the present study investigated whether feeding elicited by the mu-selective opioid agonist [D-Ala(2), NMe(4), Gly-ol(5)]-enkephalin (DAMGO) in the VTA region was altered by pretreatment into the same site with equimolar doses of either GABA(A) (bicuculline) or GABA(B) (saclofen) antagonists, and further, whether pretreatment with either general opioid or selective GABA receptor antagonists decreased feeding elicited by GABA(A) (muscimol) or GABA(B) (baclofen) agonists in the VTA region. DAMGO-induced feeding in the VTA region was dose-dependently decreased following pretreatment with either GABA(A) or GABA(B) antagonists in the absence of significant alterations in food intake by the antagonists per se. However, the presence of short-lived seizures following bicuculline in the VTA region suggests that this ingestive effect was caused by nonspecific actions. In contrast, GABA(B) receptors are involved in the full expression of mu-opioid agonist-induced feeding in this region since saclofen failed to elicit either seizure activity or a conditioned taste aversion. Pretreatment with naltrexone in the VTA region reduced intake elicited by baclofen, but not muscimol. Finally, baclofen-induced feeding was significantly reduced by saclofen, but not bicuculline, pretreatment in the VTA region. Therefore, possible coregulation between GABA(B) and opioid receptors in the VTA region, as suggested by immunocytochemical evidence, is supported by these behavioral effects upon ingestion.

Administration, Oral↗

PubMed2002

Reversal of sex differences in morphine analgesia elicited from the ventrolateral periaqueductal gray in rats by neonatal hormone manipulations.

Male rats display significantly greater analgesic responses than female rats following systemic, ventricular and intracerebral morphine administration into either the ventrolateral periaqueductal gray (vlPAG) or the rostral ventromedial medulla, and following beta-endorphin administration into the vlPAG. Although adult gonadectomy severely reduces nonopioid forms of swim stress-induced analgesia, the marked sex differences in morphine analgesia were minimally affected by either male or female adult gonadectomy. Since very little is known about neonatal effects of gonadal hormones upon sex differences in morphine analgesia elicited from the vlPAG, the present study evaluated the effects of neonatal (within 1 day of birth) castration in male rat pups relative to sham-operated controls, and systemic androgenization with testosterone propionate in female rat pups relative to vehicle-injected controls upon baseline nociceptive thresholds and morphine analgesia elicited from the vlPAG in rats tested as adults. Significant sex differences in morphine analgesia elicited from the vlPAG were observed with adult males receiving neonatal sham surgeries displaying significantly greater morphine analgesia on two nociceptive measures than adult females tested during the estrous phase and receiving neonatal vehicle injections. Neonatal gonadectomy essentially reversed the pattern of sex difference effects upon morphine analgesia elicited from the vlPAG. Neonatally-castrated male rats tested in adulthood displayed dramatic reductions in morphine analgesia elicited from the vlPAG on both the tail-flick (approximately 15-fold rightward shift) and jump (6-fold rightward shift) tests relative to sham-operated males, and essentially mirrored those of vehicle-treated females. Conversely, neonatally-androgenized female rats tested in adulthood displayed dramatic increases in morphine analgesia elicited from the vlPAG on the tail-flick (5-fold leftward shift) and jump (12-fold leftward shift) tests relative to vehicle-treated females, and approximated those observed in sham-operated males. The potent differences between neonatally-castrated and sham-operated male rats and between neonatally-androgenized and vehicle-treated female rats suggest a possible 'organizational' role of gonadal hormones in mediating sex differences in morphine analgesia elicited from the vlPAG.

Analgesics, Opioid↗

PubMed2002

Analysis of opioid receptor subtype antagonist effects upon mu opioid agonist-induced feeding elicited from the ventral tegmental area of rats.

The present study examined opioid receptor(s) mediation of feeding elicited by mu opioid agonists in the ventral tegmental area using general or selective opioid antagonist pretreatment. Naltrexone as well as equimolar doses of selective mu and kappa, but not delta opioid antagonists in the ventral tegmental area significantly reduced mu agonist-induced feeding, indicating a pivotal role for these receptor subtypes in the full expression of this response.

Animals↗

PubMed2002

Pharmacological characterization of beta-endorphin- and dynorphin A(1-17)-induced feeding using G-protein alpha-subunit antisense probes in rats.

Antisense (AS) oligodeoxynucleotides targeting G-protein alpha-subunits distinguish feeding responses of morphine and its metabolite, as well as nocturnal and deprivation-induced feeding. The present study examined whether feeding elicited by beta-endorphin (betaEND) or dynorphin A(1-17) was altered by ventricularly-applied G(i)alpha(1), G(i)alpha(2), G(i)alpha(3), G(s)alpha, G(o)alpha, G(q)alpha or G(x/z)alpha AS probes, or a nonsense (NS) control. The betaEND-induced feeding was reduced by the G(i)alpha(1) and G(x/z)alpha AS probes, and increased by G(i)alpha(2) or G(i)alpha(3) AS treatment. Dynorphin-induced feeding was attenuated by G(i)alpha(1) and G(o)alpha AS treatment. Yet, G(s)alpha or G(q)alpha AS and NS treatments failed to alter opioid agonist-induced feeding. These data provide initial characterization of potential effector signaling pathways mediating betaEND and dynorphin-induced feeding.

Animals↗

PubMed2002

Endogenous opiates and behavior: 2001.

This paper is the twenty-fourth installment of the annual review of research concerning the opiate system. It summarizes papers published during 2001 that studied the behavioral effects of the opiate peptides and antagonists. The particular topics covered this year include the molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (Section 2), and the roles of these opioid peptides and receptors in pain and analgesia (Section 3); stress and social status (Section 4); tolerance and dependence (Section 5); learning and memory (Section 6); eating and drinking (Section 7); alcohol and drugs of abuse (Section 8); sexual activity and hormones, pregnancy, development and endocrinology(Section 9); mental illness and mood (Section 10); seizures and neurologic disorders (Section 11); electrical-related activity and neurophysiology (Section 12); general activity and locomotion (Section 13); gastrointestinal, renal and hepatic functions (Section 14); cardiovascular responses (Section 15); respiration and thermoregulation (Section 16); and immunological responses (Section 17).

Animals↗

PubMed2002

Characterization of rat prepro-orphanin FQ/nociceptin((154-181)): nociceptive processing in supraspinal sites.

Orphanin FQ/nociceptin (OFQ/N), the endogenous ligand for the orphan receptor-like/kappa(3)-like opioid receptor clone, produces a variety of behavioral responses, including those associated with pronociception and antinociception. The OFQ/N precursor rattus-proOFQ (rppOFQ/N) contains several paired basic amino acids, which raises the possibility that post-translational processing can be responsible for the production of a number of additional biologically active peptide fragments. One of these putative peptides, rppOFQ/N (rppOFQ/N(154-181)), was examined for antinociceptive and pronociceptive processes in four brain sites involved in pain inhibition: the ventrolateral periaqueductal gray (vlPAG), the amygdala, the locus coeruleus (LC), and the rostroventromedial medulla (RVM). Endogenous rppOFQ/N(154-181) was identified in each region. rppOFQ/N(154-181) produced a dose-dependent antinociception in all four sites using the tailflick assay. Injections into misplaced cannula sites failed to exert effects. Antinociception in the four sites differed in their response to the opioid antagonist naloxone. Naloxone pretreatment completely blocked rppOFQ/N(154-181)-induced antinociception in the vlPAG and the amygdala, but not in the LC or RVM. In contrast rppOFQ/N(154-181) was hyperalgesic in the LC and RVM, but not in the vlPAG or amygdala. rppOFQ/N(154-181) also was compared with either its N-terminal 17-amino acid peptide (rppOFQ/N(154-170), also known as OFQ2) or its 8-amino acid C-terminal fragment (rppOFQ/N(174-181)). Although both rppOFQ/N(154-181) and rppOFQ/N(154-170) produced antinociception, the latter was less effective because the C-terminal fragment was inactive. Thus, rppOFQ/N(154-181) has complex antinociceptive and pronociceptive actions within the brain, and the pharmacological specificity of its actions differs among supraspinal sites.

Amygdala↗

PubMed2002

Dynorphin A(1-17)-induced feeding: pharmacological characterization using selective opioid antagonists and antisense probes in rats.

Ventricular administration of the opioid dynorphin A(1-17) induces feeding in rats. Because its pharmacological characterization has not been fully identified, the present study examined whether a dose-response range of general and selective opioid antagonists as well as antisense oligodeoxynucleotide (AS ODN) opioid probes altered daytime feeding over a 4-h time course elicited by dynorphin. Dynorphin-induced feeding was significantly reduced by a wide range of doses (5-80 nmol i.c.v.) of the selective kappa(1)-opioid antagonist nor-binaltorphamine. Correspondingly, AS ODN probes directed against either exons 1 and 2, but not 3 of the kappa-opioid receptor clone (KOR-1) reduced dynorphin-induced feeding, whereas a missense oligodeoxynucleotide control probe was ineffective. Furthermore, AS ODN probes directed against either exons 1 or 2, but not 3 of the kappa(3)-like opioid receptor clone (KOR-3/ORL-1) also attenuated dynorphin-induced feeding. Although the selective mu-antagonist beta-funaltrexamine (20-80 nmol) reduced dynorphin-induced feeding, an AS ODN probe directed only against exon 1 of the mu-opioid receptor clone was transiently effective. Neither general (naltrexone, 80 nmol) nor delta (naltrindole, 80 nmol)-selective opioid antagonists were particularly effective in reducing dynorphin-induced feeding, and an AS ODN probe targeting the individual exons of the delta-opioid receptor clone failed to significantly reduce dynorphin-induced feeding. These converging antagonist and AS ODN data firmly implicate the kappa(1)-opioid receptor and the KOR-1 and KOR-3/ORL-1 opioid receptor genes in the mediation of dynorphin-induced feeding.

Animals↗

PubMed1996

Excitatory amino acid antagonists in the rostral ventromedial medulla inhibit mesencephalic morphine analgesia in rats.

Supraspinal opioid analgesia is mediated in part by connections between the periaqueductal gray (PAG) and rostral ventromedial medulla (RVM). Morphine analgesia elicited from the PAG is respectively decreased by selective serotonergic and opioid receptor antagonists administered into the RVM, and increased by RVM neurotensin antagonists. Since glutamate and excitatory amino acid (EAA) receptors are also active in the RVM, the present study evaluated whether either competitive (AP7) or non-competitive (MK-801) N-methyl-D-aspartate (NMDA) antagonists or a kainate/AMPA (CNQX) antagonist microinjected into the RVM altered morphine (2.5 micrograms) analgesia elicited from the PAG as measured by the tail-flick and jump tests. Mesencephalic morphine analgesia was markedly reduced on both tests after RVM pretreatment with either AP7 (0.01-1 microgram, 0.08-7.8 nmol) or MK-801 (0.03-3 micrograms, 0.04-4.4 nmol). In contrast, small but significant reductions in mesencephalic morphine analgesia occurred on the jump test following CNQX (0.5 microgram, 2.2 nmol) in the RVM. NMDA antagonists did not markedly alter either basal nociceptive thresholds following RVM administration, or mesencephalic morphine analgesia following administration into medullary placements lateral or dorsal to the RVM. These data implicate EAA and particularly NMDA receptors in the RVM in modulating the transmission of opioid pain-inhibitory signals from the PAG.

2-Amino-5-phosphonovalerate↗

PubMed1993

Site-specific modulation of morphine and swim-induced antinociception following thyrotropin-releasing hormone in the rat periaqueductal gray.

Central administration of thyrotropin-releasing hormone (TRH) produces a short-lived antinociceptive response in rats, and also modulates opioid and non-opioid forms of antinociception. Given the presence of TRH cells, fibers and receptors in the periaqueductal gray (PAG), the present study examined the effects of TRH administered into the PAG upon antinociception following either continuous cold-water swims (CCWS, 2 degrees C for 3.5 min) or morphine (0.1-2.5 micrograms) administered into the PAG on the tail-flick and jump tests, and measured changes in core body temperatures as well. Histological examination revealed two groups in which anterior PAG placements were found rostral to the dorsal raphe nucleus, and posterior PAG placements which were at the level of this nucleus. TRH produced brief (5-15 min) but significant increases in latencies and thresholds without altering body temperature in both anterior and posterior PAG placements. Whereas TRH in anterior PAG placements dose dependently (0.1-10 micrograms) decreased CCWS antinociception on both tests, TRH in posterior PAG placements significantly increased CCWS antinociception on the jump test. TRH in both placements reduced the magnitude of CCWS hypothermia. TRH significantly potentiated the magnitude and duration of both morphine antinociception and hyperthermia in both anterior and posterior PAG placements, and shifted mesencephalic morphine's antinociceptive dose-response curve significantly to the left. These data are discussed in terms of the role of the PAG in opioid and non-opioid forms of stress-induced antinociception as well as morphine antinociception, and in terms of the roles of TRH and anterior PAG placements as potential candidates for a collateral inhibition model of antinociceptive responses.

Animals↗

PubMed1991

Gender effects and central opioid analgesia.

Central morphine analgesia is significantly greater in male than in female rats. Since mu and delta opioid receptor subtypes have been implicated in supraspinal analgesia, the present study evaluated whether gender or adult gonadectomy altered (a) analgesia on the tail-flick and jump tests following central administration of the mu-selective agonist, [D-Ala2, Me-Phe4, Gly(ol)5] enkephalin (DAMGO) and the delta-selective agonist, [D-Ser2,Leu5] enkephalin-Thr6 (DSLET) and (b) mu1, mu2 and delta opioid receptor binding. Sham-operated male rats displayed significantly greater magnitudes of peak and total analgesia than sham-operated females on the tail-flick test following DAMGO, but not DSLET. Gender differences were not observed for DAMGO and DSLET analgesia on the jump test. Gonadectomy failed to consistently affect either DAMGO or DSLET analgesia. Regression analyses failed to reflect significant shifts in the dose-response functions for either agonist on either measure. Gender differences were not observed for mu1, mu2, or delta binding in hypothalamus or cortex. These data are compared with analgesic responses sensitive to gender differences.

Analgesics, Opioid↗