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1.
Neuropsychopharmacology ; 2(3): 201-8, 1989 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2571340

RESUMEN

Extracellular single unit recording techniques were used to study the effects of selective sigma-receptor agonist [(+)-3-PPP, (+)-pentazocine, and DTG] and selective sigma-receptor antagonists (BMY 14802 and Rimcazole) on dopamine neurons of the substantia nigra. Intravenous (IV) administration of sigma agonists decreased, whereas IV administration of the sigma antagonist BMY-14802 increased the firing rate of dopamine neurons. The other sigma antagonist Rimcazole produced inconsistent changes in dopamine unit activity. These data, in conjunction with anatomic data suggesting sigma receptor localization on dopamine neurons in the substantia nigra (Gundlach et al: J Neurosci 6:1757-1770, 1986; Graybiel et al: Soc Neurosci Abstr 13:28, 1987) demonstrate a relationship of the sigma receptor with the dopamine system and further suggest a model system to study agonist-antagonist interactions of sigma ligands. The selective phencyclidine (PCP) agonist MK-801 was equipotent to PCP in regard to stimulatory properties on dopamine neurons. However, the relative potencies do not correspond to their relative binding affinities, suggesting that non-PCP-receptor properties may mediate this effect.


Asunto(s)
Anticonvulsivantes/farmacología , Dibenzocicloheptenos/farmacología , Dopamina/fisiología , Neuronas/fisiología , Fenciclidina/farmacología , Sustancia Negra/fisiología , Animales , Ansiolíticos/farmacología , Antipsicóticos/farmacología , Carbazoles/farmacología , Membrana Celular/metabolismo , Maleato de Dizocilpina , Dopaminérgicos/farmacología , Masculino , Neuronas/efectos de los fármacos , Pentazocina/farmacología , Piperidinas/farmacología , Pirimidinas/farmacología , Ratas , Ratas Endogámicas , Receptores de Neurotransmisores/fisiología , Receptores Opioides/fisiología , Receptores de Fenciclidina , Receptores sigma , Sustancia Negra/efectos de los fármacos
2.
Neuropsychopharmacology ; 1(4): 321-7, 1988 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-2855202

RESUMEN

Research on the sigma receptor, a binding site associated with drug-induced psychotomimetic behaviors, has been hampered because most sigma agonists also interact with the phencyclidine (PCP) receptor. (+)-Pentazocine, a human psychotogen, is a selective sigma receptor ligand. To demonstrate sigma receptor activities, we studied the behavioral and electrophysiologic actions for (+)-pentazocine. In the behavioral drug discrimination procedure in which rats were trained to discriminate between 2.0 mg/kg (5.59 mumol/kg) (+)-pentazocine and saline, (+)-pentazocine produced dose-related increases in the percentage of trials completed on the (+)-pentazocine lever. At a dose of 1.0 mg/kg (3.29 mumol/kg) (+)-N-allylnormetazocine generalized completely to (+)-pentazocine. By contrast, PCP only partially generalized. In the visual evoked potential test, these compounds produced a significant dose-dependent slowing of the N2 latency. This response was prevented by haloperidol pretreatment. These results demonstrate pharmacologic actions for the selective sigma receptor ligand (+)-pentazocine and suggest some overlapping pharmacologic properties of the sigma and PCP receptor sites despite differences in central nervous system distribution.


Asunto(s)
Reacción de Prevención/efectos de los fármacos , Encéfalo/metabolismo , Aprendizaje Discriminativo/efectos de los fármacos , Potenciales Evocados Visuales/efectos de los fármacos , Pentazocina/farmacología , Fenciclidina/farmacología , Receptores de Neurotransmisores/metabolismo , Receptores Opioides/metabolismo , Animales , Masculino , Membranas/metabolismo , Pentazocina/metabolismo , Fenazocina/análogos & derivados , Fenazocina/farmacología , Fenciclidina/metabolismo , Conejos , Ratas , Ratas Endogámicas F344 , Receptores de Fenciclidina , Receptores sigma , Valores de Referencia
3.
Psychopharmacology (Berl) ; 116(3): 243-8, 1994 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-7892412

RESUMEN

This study compared the potency of mixed-action opioids (i.e., agonist-antagonists) and pure antagonists to block the discriminative stimulus effects of spiradoline, a kappa-opioid agonist. Rats were trained to discriminate between 3.0 mg/kg spiradoline and saline (SC) in a two-choice discrete-trial procedure. Graded doses of test drugs were administered in combination with 3.0 mg/kg spiradoline and the dose that reduced selection of the spiradoline-appropriate choice lever by 50% (AD50) was calculated. Ten drugs blocked the discriminative effects of spiradoline in an orderly dose-dependent manner. They spanned a 150-fold potency range from diprenorphine (5 times as potent as naloxone) to nalbuphine (0.03 times as potent as naloxone). Antagonism was stereoselective: 0.1-1.0 mg/kg (-)-N-allylnormetazocine (NANM) reduced spiradoline-appropriate responding by 50% whereas 3.0 mg/kg (+)-NANM did not. (-)-Pentazocine (0.1-10 mg/kg) and butorphanol (0.1-3.0 mg/kg) also did not block the discriminative effects of spiradoline. Antagonism was surmountable when graded doses of spiradoline were tested with a fixed dose of diprenorphine, naloxone, or levallorphan. Apparent pKB values derived from the interactions between those three drugs and spiradoline were in accord with relative antagonist potencies based upon the AD50s. Because the potency of a competitive antagonist is determined by its receptor affinity, the relative potencies of mixed-action opioids and pure antagonists in blocking the discriminative stimulus effects of spiradoline can provide an estimate of the relative in vivo affinities of these drugs for the kappa-opioid receptor.


Asunto(s)
Analgésicos/antagonistas & inhibidores , Discriminación en Psicología/efectos de los fármacos , Pirrolidinas/antagonistas & inhibidores , Receptores Opioides kappa/agonistas , Analgésicos/farmacología , Animales , Reacción de Prevención/efectos de los fármacos , Aprendizaje Discriminativo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Masculino , Narcóticos/farmacología , Fenazocina/análogos & derivados , Fenazocina/farmacología , Pirrolidinas/farmacología , Ratas , Ratas Sprague-Dawley , Estereoisomerismo
4.
Psychopharmacology (Berl) ; 105(4): 447-52, 1991.
Artículo en Inglés | MEDLINE | ID: mdl-1663252

RESUMEN

This study represents the initial step in assessing the discriminative effects of spiradoline (U62,066), a potent congener of the selective kappa-opioid agonist, U50,488. Separate groups of rats were trained to discriminate between SC injections of saline and either 3.0 mg/kg spiradoline or 3.0 mg/kg morphine in a discrete-trial shock-avoidance/escape procedure. Spiradoline-trained rats generalized completely to U50,488 (ED50S for spiradoline and U50,488 were 0.66 and 8.71 mg/kg, respectively), but selected the choice lever appropriate for saline in generalization tests with graded doses of morphine, phencyclidine, and agonist-antagonist opioids with varying degrees of kappa activity, ethylketocyclazocine, nalorphine, and butorphanol. Morphine-trained rats did not generalize to spiradoline. Naltrexone (0.01 or 0.1 mg/kg) blocked surmountably the discriminative effects of both spiradoline and morphine, but was approximately 10-fold less potent against spiradoline. These results indicate that the discriminative effects of spiradoline are mediated by kappa-opioid receptors; meaningful mu-opioid and PCP/sigma components of action were not in evidence. The potency and apparent pharmacological selectivity of spiradoline suggest the potential value of this drug for studying kappa-opioid-mediated stimulus control of behavior.


Asunto(s)
Discriminación en Psicología/efectos de los fármacos , Pirrolidinas/farmacología , Receptores Opioides/efectos de los fármacos , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero , Animales , Butorfanol/farmacología , Discriminación en Psicología/fisiología , Etilcetociclazocina/farmacología , Generalización del Estimulo , Masculino , Morfina/farmacología , Nalorfina/farmacología , Fenciclidina/farmacología , Ratas , Ratas Endogámicas , Tiempo de Reacción , Receptores Opioides kappa , Receptores Opioides mu
5.
Psychopharmacology (Berl) ; 91(1): 5-9, 1987.
Artículo en Inglés | MEDLINE | ID: mdl-3029793

RESUMEN

Recent studies have identified a stereospecific (+)-NANM binding site that binds psychotomimetic opioids and phencyclidine (PCP) but has a distribution in brain different from the PCP binding site. Since (+)-NANM has no opioid activity and (-)-NANM has opioid activity, rats were trained to discriminate (+)-NANM from saline in order to develop an ability to distinguish the (+)-NANM cues from other opioid agonist and antagonist activities. Cyclazocine, PCP, and ketamine all produced (+)-NANM-like stimuli in a dose-dependent manner. Behaviorally, cyclazocine and PCP are equipotent to (+)-NANM whereas ketamine is 6.7 times less potent than (+)-NANM. Pentazocine had the highest affinity for the (+)-[3H]NANM binding site, yet did not produce (+)-NANM-like discriminative stimuli. By contrast, ketamine had the lowest binding affinity for the (+)-[3H]NANM binding site and did produce (+)-NANM-like discriminative stimuli. Drug discrimination potencies relative to (+)-NANM were not predictive of relative binding affinities at (+)-NANM or PCP binding sites, although there was a trend toward a stronger correlation with the PCP binding site. Therefore, the discriminative stimulus properties of (+)-NANM cannot be explained by pharmacologic actions at either (+)-NANM or PCP binding sites alone, and may involve concurrent actions at both sites.


Asunto(s)
Encéfalo/metabolismo , Aprendizaje Discriminativo , Fenazocina/análogos & derivados , Fenciclidina/metabolismo , Receptores de Neurotransmisores/metabolismo , Animales , Ciclazocina/farmacología , Ketamina/farmacología , Masculino , Pentazocina/farmacología , Fenazocina/metabolismo , Fenazocina/farmacología , Ratas , Ratas Endogámicas F344 , Receptores de Fenciclidina , Estereoisomerismo
6.
Peptides ; 6 Suppl 2: 171-5, 1985.
Artículo en Inglés | MEDLINE | ID: mdl-2867529

RESUMEN

The analgesic activity of the prototypic opioid peptides for the mu (D-Ala2-Me-Phen4-Gly-ol5-enkephalin [DAGO]) kappa (Dynorphin 1-13), delta (D-Ala2-D-Leu5-enkephalin [DADLE]), or epsilon (beta-endorphin) receptor was assessed in a rat tooth pulp stimulation procedure. All opioid peptides tested and the opioid alkaloid U50, 488H (kappa receptor agonist) significantly elevated response thresholds. The rank order of potency based on the Minimum Effective Dose values was beta-endorphin greater than DAGO = dynorphin A (1-13) amide greater than DADLE greater than dynorphin A (1-13) greater than U50,488H. Based on absolute magnitude, the rank order of dose response slopes was DAGO greater than U50,488H greater than dynorphin A (1-13) amide greater than beta-endorphin greater than DADLE. Dynorphin A (1-13) produced the shallowest dose response slope and the magnitude of response threshold was the lowest for all compounds tested. Finally, the general conclusion that mu agonists are effective against noxious stimuli derived from thermal, chemical, and mechanical is extended by our data to include electrical sources derived from tooth pulp stimulation; kappa agonists are effective against noxious stimuli derived from chemical, mechanical, and electrical sources (tooth pulp stimulation) and delta agonists are effective analgesics against thermal, chemical and electrical stimuli (tooth pulp stimulation).


Asunto(s)
Analgésicos , Endorfinas/uso terapéutico , Dolor/tratamiento farmacológico , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero , Animales , Pulpa Dental/inervación , Dinorfinas/uso terapéutico , Estimulación Eléctrica , Encefalina Ala(2)-MeFe(4)-Gli(5) , Encefalina Leucina/análogos & derivados , Encefalina Leucina/uso terapéutico , Leucina Encefalina-2-Alanina , Encefalinas/uso terapéutico , Masculino , Fragmentos de Péptidos/uso terapéutico , Pirrolidinas/uso terapéutico , Ratas , Ratas Endogámicas , betaendorfina
7.
Brain Res ; 251(2): 259-76, 1982 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-7139326

RESUMEN

Serotonergic neurons within nucleus raphe pallidus (NRP) of freely moving cats initially were distinguished by their slow (less than 8 Hz), regular discharge and long duration (mean = 2.3 ms) action potentials. The activity of serotonergic NRP neurons was highest during active waking (mean = 4.85 +/- 0.37 spikes/s) and gradually slowed, with little change in firing pattern, during the transition from waking through slow wave sleep (middle of SWS: mean = 3.76 +/- 0.36 spikes/s). In REM sleep there was a precipitous decrease in firing rate (mean = 0.92 +/- 0.23 spikes/s) and loss of discharge regularity. Although there was no significant difference in firing rate between active and quiet waking, discharge rates were significantly increased during transient elevations of the EMG, but these rate increases usually were associated with specific motor behaviors only. The activity of serotonergic NRP neurons during SWS was not related to the occurrence of either sleep spindles in the cortical EEG or PGO waves recorded from the lateral geniculate nucleus. These neurons also were relatively unresponsive to phasic auditory or visual stimuli, with most of the neurons examined showing weak excitatory responses. Activity of all serotonergic NRP neurons tested was suppressed (mean = -81.3 +/- 4.3%) by the serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (250 micrograms/kg, i.m.). The results of this study are compared with those previously reported for serotonergic neurons in the dorsal raphe nucleus of freely moving cats and the issue of homogeneity in central serotonergic systems is discussed.


Asunto(s)
Tronco Encefálico/fisiología , Neuronas/fisiología , Núcleos del Rafe/fisiología , Serotonina/fisiología , Estimulación Acústica , Potenciales de Acción , Animales , Gatos , Femenino , Cuerpos Geniculados/fisiología , Metoxidimetiltriptaminas/farmacología , Actividad Motora , Movimiento , Estimulación Luminosa , Sueño , Vigilia
8.
Brain Res ; 181(2): 425-32, 1980 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-7188678

RESUMEN

Diurnal variations were observed in the EEG power spectra of REM sleep and non-REM (NREM) sleep in the rat. Diurnal variations occurred in peak EEG frequency and spectral power (0-27 Hz and 5-9 Hz bands) during REM sleep. During NREM sleep diurnal variations were observed in spectral power in the 0-27 Hz and 0-4 Hz bands. The significance of these findings is discussed in terms of correlative data involving diurnal variations in neurotransmitters and hormones, all of which have been implicated in the induction or maintenance of sleep states.


Asunto(s)
Ritmo Circadiano , Electroencefalografía , Sueño REM/fisiología , Animales , Potenciales Evocados , Femenino , Lóbulo Frontal/fisiología , Lóbulo Parietal/fisiología , Ratas , Vigilia/fisiología
9.
Brain Res ; 291(1): 63-72, 1984 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-6697186

RESUMEN

The influence of chloral hydrate anesthesia on the spontaneous activity and responsiveness of serotonergic neurons was examined by administering chloral hydrate (300 mg/kg, i.p.) to freely moving cats from which serotonergic unit activity in the dorsal raphe nucleus (DRN) was being recorded. Although chloral hydrate administration produced a surgical level of anesthesia within 15 min following injection, it produced only a small decrease (approximately 20%) in the spontaneous activity of DRN serotonergic neurons. In contrast, the responsiveness of these same neurons was greatly altered by chloral hydrate administration. By examining the same neuron before and after chloral hydrate injection, it was found that chloral hydrate anesthesia completely abolished the excitatory responses of DRN serotonergic neurons to auditory and visual stimuli, as well as their excitatory response to electrical stimulation of the gigantocellular tegmental field (FTG) in the pontine reticular formation. On the other hand, the inhibition of serotonergic neuron firing resulting from systemic administration of WB 4101 (1.0 mg/kg, i.p.), a selective alpha 1 adrenergic receptor antagonist, was greatly potentiated by chloral hydrate anesthesia. Therefore, these data indicate that chloral hydrate anesthesia produces profound changes in the physiological and pharmacological responses of central serotonergic neurons which are not predictable by examination of spontaneous activity alone. Furthermore, as discussed, it it not clear to what extent these confounding influences might generalize to other anesthetized or immobilized preparations. Thus, beyond the obvious advantage which allows for the study of relationships between neuronal activity and behavior, single unit studies conducted in awake, freely moving animals also may be of greater value for basic physiological and pharmacological studies.


Asunto(s)
Anestesia General , Tronco Encefálico/fisiología , Hidrato de Cloral , Núcleos del Rafe/fisiología , Serotonina/fisiología , Animales , Gatos , Estimulación Eléctrica , Potenciales Evocados Auditivos , Potenciales Evocados Visuales , Tegmento Mesencefálico/fisiología
10.
Brain Res ; 260(2): 317-21, 1983 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-6831204

RESUMEN

The activity of dopaminergic neurons in the substantia nigra was recorded from freely moving cats during feeding and satiety, and following injections of glucose. At no time during feeding or in the postprandial satiety period was there a significant increase or decrease in firing rate of these neurons relative to baseline. Additionally, no change in firing rate was observed following injections of glucose (300, 500 and 1000 mg/kg) or glucose in combination with insulin (300 mg/kg glucose and 0.8 units/kg insulin).


Asunto(s)
Glucemia/metabolismo , Dopamina/fisiología , Ingestión de Alimentos , Saciedad/fisiología , Sustancia Negra/fisiología , Animales , Gatos , Potenciales Evocados , Hambre/fisiología , Neuronas/fisiología
11.
Brain Res ; 258(2): 217-28, 1983 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-6824912

RESUMEN

Single unit activity of dopaminergic neurons in the substantia nigra was recorded in freely moving cats under a variety of conditions. These neurons displayed their highest discharge rate during active waking (3.68 +/- 0.30 spikes/s), which was 20% greater than their discharge rate during quiet waking (3.07 +/- 0.20). Although these cells fired somewhat faster during active waking, their activity displayed no correlation with phasic EMG changes, and, in general, their activity showed little relationship to overt behavioral changes. As the cat progressed from quiet waking through slow-wave sleep and REM sleep there was no significant change in either the rate or pattern of firing of dopaminergic neurons. In addition, no correlation was observed between the activity of these neurons and either sleep spindles or PGO waves. These neurons did respond, however, to the repeated presentation of a click or light flash with excitation followed by inhibition, with no evidence of habituation. One of the most impressive changes in dopaminergic unit activity was a large decrease in association with orienting responses. This was seen in over 50% of the cells in which this relationship was examined. As the behavioral orientation habituated with repeated stimulus presentation, so did the associated dopaminergic unit suppression. In conclusion, dopaminergic neurons maintain a remarkably constant rate and pattern of firing across a variety of behaviors and states. However, this stability can be dramatically altered under special circumstances, such as during and following orienting responses.


Asunto(s)
Conducta Animal , Dopamina/fisiología , Actividad Motora , Neuronas/fisiología , Sustancia Negra/fisiología , Animales , Apomorfina/farmacología , Gatos , Femenino , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Sueño/fisiología , Sueño REM/fisiología , Vigilia/fisiología
12.
Brain Res ; 277(1): 150-4, 1983 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-6640288

RESUMEN

The response of dopaminergic neurons of the substantia nigra pars compacta to auditory clicks continuously presented across the sleep-wake cycle was studied in cats. The initial excitatory followed by inhibitory response to the click which occurred during quiet waking diminished as the cat progressed into slow-wave sleep and was absent during REM sleep. Upon awakening from REM sleep, dopamine neurons once again displayed an excitatory/inhibitory response to the clicks, implying that the decrease across the sleep-wake cycle was not attributable to long-term habituation.


Asunto(s)
Percepción Auditiva/fisiología , Dopamina/fisiología , Fases del Sueño/fisiología , Sustancia Negra/fisiología , Animales , Apomorfina/farmacología , Vías Auditivas/fisiología , Gatos , Electrofisiología , Femenino , Inhibición Neural , Serotonina/fisiología , Sueño REM/fisiología
13.
Brain Res ; 279(1-2): 77-84, 1983 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-6315184

RESUMEN

Single unit activity of serotonergic neurons in the dorsal raphe nucleus of freely moving cats was recorded in experiments which manipulated central or peripheral motor systems. Unilateral microinjections of the cholinomimetic agent, carbachol, into the pontine tegmentum, produced muscle atonia. During these periods of drug-induced atonia, the activity of serotonergic neurons was reduced 97% below pre-drug baseline rates. In experiments where microinjections of carbachol did not produce muscle atonia, no significant change occurred in serotonergic unit discharge rate. Muscle tonus was also altered by systemic injections of mephenesin, a centrally acting muscle relaxant. A low dose of mephenesin (50 mg/kg) produced mild atonia which was correlated with a 16% reduction in serotonergic neuron discharge rate relative to pre-drug baseline. A higher dose of mephenesin (150 mg/kg) produced complete atonia, during which serotonergic unit activity was reduced by 68% below baseline firing rate. To distinguish between centrally and peripherally induced atonia, we injected either succinylcholine or dantrolene, systemically. These are both drugs whose muscle relaxant properties are known to be mediated by peripheral mechanisms. In neither case was a change in serotonergic unit discharge rate seen following drug-induced atonia. These data demonstrate that manipulation of central, but not peripheral, motor systems can profoundly affect the activity of serotonergic neurons of the dorsal raphe nucleus. Alternate hypotheses are also discussed.


Asunto(s)
Tronco Encefálico/fisiología , Actividad Motora/fisiología , Músculos/inervación , Núcleos del Rafe/fisiología , Transmisión Sináptica , Animales , Nivel de Alerta/fisiología , Carbacol/farmacología , Gatos , Relación Dosis-Respuesta a Droga , Electromiografía , Potenciales Evocados/efectos de los fármacos , Femenino , Mefenesina/farmacología , Mesencéfalo/fisiología , Tono Muscular/efectos de los fármacos , Puente/fisiología , Serotonina/fisiología , Sueño REM/fisiología , Transmisión Sináptica/efectos de los fármacos
14.
Brain Res ; 329(1-2): 350-3, 1985 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-3978457

RESUMEN

Quantitative analyses of the single unit responses to sensory stimuli were made in caudate nucleus neurons in the unanesthetized freely moving cat. Over half of the cells were responsive to repetitive presentation of simple sensory stimuli. Typically, neurons gave similar responses to both auditory (click) and visual (flash) stimuli. This study confirms previous reports of the polysensory response characteristics of caudate nucleus neurons, and extends these observations to the freely moving animal.


Asunto(s)
Percepción Auditiva/fisiología , Núcleo Caudado/fisiología , Percepción de Movimiento/fisiología , Animales , Mapeo Encefálico , Gatos , Femenino , Habituación Psicofisiológica/fisiología , Núcleos del Rafe/fisiología , Tiempo de Reacción/fisiología , Sustancia Negra/fisiología , Núcleos Talámicos/fisiología
15.
Eur J Pharmacol ; 163(1): 167-70, 1989 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-2568265

RESUMEN

Extracellular recording techniques were used to study the effects of the selective sigma receptor agonist (+)-[3H]3-(3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3-PPP) and selective sigma receptor antagonist BMY 14802 on dopamine (DA) neurons of the substantia nigra. Intravenous administration of (+)-3-PPP produced a dose-dependent inhibition of DA neuron firing rate. Complete inhibition of DA neurons produced by (+)-3-PPP could be completely reversed by administration of BMY 14802. Also, pretreatment with BMY 14802 shifted the (+)-3-PPP dose response curve to the right. These data demonstrate a relationship of the sigma receptor with the dopamine system and further suggest a model system to study agonist/antagonist interactions of sigma ligands.


Asunto(s)
Dopamina/fisiología , Narcóticos/farmacología , Neuronas/fisiología , Receptores Opioides/fisiología , Animales , Antipsicóticos/farmacología , Técnicas In Vitro , Masculino , Membranas/metabolismo , Microelectrodos , Antagonistas de Narcóticos , Piperidinas/farmacología , Pirimidinas/farmacología , Ratas , Ratas Endogámicas , Receptores Opioides delta , Espiperona/metabolismo
16.
Eur J Pharmacol ; 141(1): 163-6, 1987 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-2822445

RESUMEN

The role of the dopaminergic, noradrenergic and serotonergic systems in the production of the discriminative stimulus (DS) properties of the sigma receptor agonist (+)-N-allylnormetazocine [(+)-NANM/(+)-SKF 10,047] was measured in rats. The partial generalization of the noradrenergic agonist clonidine with (+)-NANM and partial antagonism of (+)-NANM by yohimbine suggest that the noradrenergic system may play a role in (+)-NANM DS. Activation of the dopaminergic system by apomorphine did not produce (+)-NANM DS however, haloperidol, which binds to the sigma receptor with high affinity, antagonized (+)-NANM DS. These data suggest that the haloperidol antagonism of (+)-NANM DS is a function of antagonism at the sigma receptor rather than antagonism at the dopamine receptor. Since yohimbine does not bind to the sigma receptor, yohimbine antagonizes (+)-NANM by a mechanism different from that of haloperidol. There was no evidence to suggest serotonergic mediation of (+)-NANM DS.


Asunto(s)
Aminas Biogénicas/fisiología , Discriminación en Psicología/efectos de los fármacos , Fenazocina/análogos & derivados , Receptores Opioides/metabolismo , Animales , Apomorfina/farmacología , Química Encefálica/efectos de los fármacos , Haloperidol/farmacología , Masculino , Metisergida/farmacología , Fenazocina/farmacología , Ratas , Ratas Endogámicas F344 , Receptores Opioides delta , Yohimbina/farmacología
17.
Eur J Pharmacol ; 81(4): 677-80, 1982 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-7117390

RESUMEN

A comparison was made of the effects of 5-MeoDMT or LSD on serotonergic unit activity in the dorsal raphe nucleus (DRN) and nucleus raphe pallidus (NRP) of freely moving cats. NRP neurons were substantially less responsive than DRN neurons to both drugs. NRP neurons were unresponsive to behaviorally effective low doses of these drugs whereas the activity of DRN neurons was strongly depressed. These data are discussed in terms of autoregulatory control of serotonergic neurons.


Asunto(s)
Dietilamida del Ácido Lisérgico/farmacología , Bulbo Raquídeo/metabolismo , Metoxidimetiltriptaminas/farmacología , Neuronas/efectos de los fármacos , Serotonina/análogos & derivados , Serotonina/fisiología , Animales , Gatos , Femenino , Núcleos del Rafe/efectos de los fármacos
18.
Eur J Pharmacol ; 231(3): 473-6, 1993 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-8095467

RESUMEN

I.v. administration of U-50,488H after i.v. saline pretreatment produced occasional high-voltage EEG slow-wave bursts that were associated with relatively small increases in spectral power in the 2.5-7.5 Hz band as a spectral peak and with behavioral incidents of sedation, ataxia, ptosis, straub tail, hunching of the back, and backing-up. After pretreatment with the sigma antagonists rimcazole and DuPont Merck S-7389-4, U-50,488H administration produced significantly larger increases in absolute EEG spectral power, both over the 1-50 Hz range and in the 2.5-5.0 and 5.0-7.5 Hz bands, than after saline pretreatment; rimcazole pretreatment eliminated U-50,488H-induced incidents of ataxia, ptosis, hunching of the back and backing-up. In summary, effects of U-50,488H on EEG, EEG power spectra and behavior may reflect interactions between kappa opioid and sigma (non-opioid) receptor-effector systems.


Asunto(s)
Antihipertensivos/farmacología , Antipsicóticos/farmacología , Conducta Animal/efectos de los fármacos , Carbazoles/farmacología , Electroencefalografía/efectos de los fármacos , Pirrolidinas/farmacología , Receptores sigma/antagonistas & inhibidores , 3,4-Dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclohexil)-bencenacetamida, (trans)-Isómero , Animales , Interacciones Farmacológicas , Femenino , Inyecciones Intravenosas , Ratas , Ratas Sprague-Dawley
19.
Life Sci ; 39(26): 2611-5, 1986 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-3796207

RESUMEN

In rats trained to discriminate the prototypic sigma receptor agonist, (+)-N-Allylnormetazocine [(+)-N-Allylnormetazocine [(+)-NANM/SKF 10,047], from saline, the (+)- but not the (-)-isomer of 3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (3-PPP) produced (+)-NANM-like discriminative stimuli. (+)-3-PPP binds stereo selectively to the (+)-NANM binding site, but not to the phencyclidine binding site. Additionally, phencyclidine was found to produce (+)-NANM-like discriminative stimuli. Although the 3-PPP isomers were shown to produce changes in central dopaminergic activity (Hjorth et al. Life Sci 37, 673, 1985), the discriminative stimulus properties of (+)-3-PPP are apparently not mediated via the dopaminergic system. This hypothesis is supported by the fact that apomorphine did not produce (+)-NANM-like discriminative stimuli. These stimuli are thus non-dopaminergic and may be due to the (+)-3-PPP actions at the sigma binding site. However, it is possible that (+)-NANM, PCP, and (+)-3-PPP may have common non-sigma pharmacologic properties that account for the similar discriminative stimulus properties of these compounds.


Asunto(s)
Aprendizaje Discriminativo/efectos de los fármacos , Fenazocina/análogos & derivados , Piperidinas/farmacología , Animales , Apomorfina/farmacología , Relación Dosis-Respuesta a Droga , Isomerismo , Masculino , Fenazocina/farmacología , Fenciclidina/farmacología , Ratas , Ratas Endogámicas F344
20.
Pharmacol Biochem Behav ; 47(3): 575-8, 1994 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8208776

RESUMEN

The results of studies on mice indicate that the antinociceptive effects of kappa-opioid agonists are due, in part, to activation of the 5-HT2 type of serotonin receptor. One objective of this study was to determine if the discriminative effects of spiradoline, a kappa-opioid agonist, are mediated by 5-HT2 receptors in rats also. A second objective was to confirm findings that dopamine receptor antagonists produce spiradoline-like discriminative effects (Ohno et al., 1992). Rats were trained to discriminate between spiradoline (3.0 mg/kg) and saline in a discrete-trial avoidance/escape procedure. In subsequent tests of stimulus generalization, the discriminative effects of spiradoline were not mimicked by fenfluramine (0.3-10 mg/kg) or fluoxetine (1.0-10 mg/kg), drugs that enhance serotonergically mediated neurotransmission, nor were they blocked by the 5-HT2 antagonists pirenperone (0.01-1.0 mg/kg) and ketanserin (0.1-10 mg/kg), or potentiated by fluoxetine pretreatment. Neither the dopamine receptor antagonists haloperidol (0.01-0.3 mg/kg) and sulpiride (3.0-100 mg/kg) nor the agonists apomorphine (0.03-0.3 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) engendered spiradoline-like discriminative effects. These results demonstrate further the pharmacological specificity of the discriminative effects of spiradoline, but provide no evidence for mediation by serotonergic or dopaminergic systems.


Asunto(s)
Analgésicos/farmacología , Monoaminas Biogénicas/fisiología , Discriminación en Psicología/efectos de los fármacos , Pirrolidinas/farmacología , Receptores Opioides kappa/efectos de los fármacos , Animales , Reacción de Prevención/efectos de los fármacos , Antagonistas de Dopamina , Fenfluramina/farmacología , Fluoxetina/farmacología , Generalización del Estimulo/efectos de los fármacos , Ketanserina/farmacología , Masculino , Piperidinas/farmacología , Ratas , Ratas Sprague-Dawley , Serotonina/fisiología , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Transmisión Sináptica/efectos de los fármacos
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