PubMed Health⌕ Search

Biomedical subjects

J D Belluzzi

Publications and source records attributed to J D Belluzzi.

At least 19 recordsLinked to original sources
PubMed1991

Naloxone blockade of amphetamine place preference conditioning.

Amphetamine and naloxone were examined in place conditioning, in order to study possible interactions between endogenous opioids and catecholamines in reinforcement. After initial preferences were determined, animals were conditioned with amphetamine alone (1.0 mg/kg SC), naloxone alone (0.02, 0.2 or 2.0 mg/kg SC) or combinations of amphetamine plus naloxone. A reliable, long-lasting preference for the compartment associated with amphetamine was observed, reflecting the reinforcing properties of this drug. No preference or aversion was observed in animals that received saline in both compartments. Naloxone (0.02, 0.2 and 2.0 mg/kg) produced a dose-dependent place aversion; while the lowest dose had effects similar to saline, the higher doses produced significant place aversions. Naloxone, at all three doses examined, prevented the ability of amphetamine to produce a place preference. Thus, the lowest dose of naloxone, having no effects alone in place conditioning was still able to block the reinforcing effects of amphetamine. These results suggest that the reinforcing effects of amphetamine are dependent on activation of opiate receptors, and provide further evidence that interactions between endogenous opioids and catecholamines may be important in reinforcement.

Amphetamine↗
PubMed1989

Opiate antagonists and self-stimulation: extinction-like response patterns suggest selective reward deficit.

The present study investigated the response decrement patterns produced by opiate antagonists on intracranial self-stimulation behavior, in order to determine if these drugs affect the reinforcement value of the stimulation or interfere with the ability of the animal to respond. Male rats lever-pressed in 60-min sessions on a continuous reinforcement schedule for self-stimulation of the nucleus accumbens. Naloxone (2.0 and 20 mg/kg) and naltrexone (2.0 and 20 mg/kg) suppressed self-stimulation only after a significant delay, in an extinction-like response decrement pattern, mimicking the effects of reductions in current intensity (75% and 50% of baseline). The increasing behavioral effects characteristic of the extinction pattern were observed despite the fact that testing began after the time point at which maximal suppression of self-stimulation occurs with these drugs, and when brain concentrations of these drugs were declining. Since normal responding was observed for several minutes after the beginning of the session, the results may explain why long sessions are necessary to observe suppression of self-stimulation by opiate antagonists. The extinction-like pattern produced by these drugs suggests that opiate antagonists suppress self-stimulation by reducing the reinforcement value of the stimulation, rather than by interfering with the ability of the animal to respond. These findings are consistent with a role for endogenous opioid peptides in brain stimulation reward.

Animals↗
PubMed1989

Effects of opiate antagonists and their quaternary analogues on nucleus accumbens self-stimulation.

Naloxone and naltrexone were compared with their quaternary analogues naloxone methobromide and naltrexone methobromide for efficacy in suppressing intracranial self-stimulation behavior. These quaternary analogues effectively block opiate receptors in the periphery, but since they do not readily cross the blood-brain barrier they have little effect on central receptors. Rats with electrodes in the nucleus accumbens were trained to self-stimulate in daily 60-min sessions. Naloxone (0.2, 2.0 and 20 mg/kg) and naltrexone (20 mg/kg) potently suppressed self-stimulation behavior. In contrast, neither naloxone methobromide (0.2 and 20 mg/kg) nor naltrexone methobromide (20mg/kg) had any significant effects on this behavior. These results suggest that blockade of peripheral opiate receptors alone is insufficient to suppress self-stimulation, and therefore support the idea that opiate antagonists suppress self-stimulation by blockade of central receptors that mediate reinforcement.

Animals↗
PubMed1989

Naloxone suppression of self-stimulation is independent of response difficulty.

The action of the opiate antagonist naloxone on relatively easy (nose-poke) and relatively difficult (lever-press) self-stimulation behaviors was compared, in order to determine if opiate antagonists suppress self-stimulation by interfering with the ability of the animal to respond, or by reducing the reinforcement value of the stimulation. Naloxone (0.2, 2.0 and 20 mg/kg) significantly suppressed both nose-poking and lever-pressing self-stimulation rates, and the degree of suppression was virtually identical for both tasks at all doses examined. If naloxone had interfered with the ability of the animal to respond, then lever-pressing--which requires more motor output than nose-poking--should have been more suppressed than nose-poking. The results suggest that opiate antagonists do not interfere with the ability of the animal to respond, and are therefore consistent with the hypothesis that these drugs reduce the reinforcement value of the stimulation.

Animals↗
PubMed1988

BAM-18: analgesia, hyperalgesia and locomotor effects.

BAM-18, a proenkephalin A-derived opioid peptide, is widely distributed throughout rat CNS and displays high affinity for both mu and kappa opioid receptors. In the present study, BAM-18 was tested in two analgesia paradigms, tail-flick and hot-plate. Injections were centrally administered through a chronically implanted unilateral cannula in the lateral ventricle. In the tail-flick, low doses of BAM-18 (5 micrograms) produced a hyperalgesia while high doses of BAM-18 (50 micrograms) produced an analgesic response. Naloxone (10 mg/kg, s.c.) reversed the BAM-18-induced analgesia and unmasked a persistent hyperalgesia. Morphine-induced (1 microgram) analgesia was completely reversed by 5 micrograms BAM-18. In the hot-plate test, high doses of BAM-18 produced analgesia, with no hyperalgesia observed at any dose. Naloxone reversed the BAM-18-induced analgesia. The locomotor effects of BAM-18 did not differ from those of morphine except in effective dose (50 micrograms vs. 5 micrograms, respectively). Opioid and non-opioid effects of BAM-18 are discussed and compared with other endogenous peptides.

Amino Acid Sequence↗
PubMed1986

Intraventricular administration of BAM-18: antinociceptive and locomotor activity in the rat.

BAM-18, a new endogenous opioid containing 18 amino acid residues, was tested in 3 behavioral paradigms. Tail-flick analgesia, a spinally mediated response, hot-plate analgesia, a centrally mediated response, and open-field locomotor activity. Rats were stereotaxically implanted with a unilateral cannula aimed at the lateral ventricle. Following recovery, each animal was tested in one of the paradigms after receiving an intraventricular injection of BAM-18, morphine or the Ringer's vehicle. BAM-18 produced significant tail-flick analgesia only at doses (50 micrograms) 50 times higher than those needed with morphine (1 microgram). BAM-18 produced an extended hyperalgesia at lower doses (5 micrograms) that was also seen transiently at the high dose. The analgesia but not the hyperalgesia was reversed by naloxone (10 mg/kg, s.c.). BAM-18 produced significant naloxone-reversible hot-plate analgesia, but again it was less potent than morphine (50 micrograms for BAM-18 vs. 5 micrograms for morphine). There was no evidence of hyperalgesia in this paradigm. Locomotor activity, following 50 micrograms of BAM-18, resembled control injections for the first 18 minutes, then became reduced in a manner similar to morphine (5 micrograms). This reduction in activity was completely reversed by naloxone. These data suggest that BAM-18 is indeed an opioid molecule but is at least 10 times less potent at altering behavior than morphine.

Analgesia↗
PubMed1985

Reinforcement delay of one second severely impairs acquisition of brain self-stimulation.

The effect of delayed reinforcement on the acquisition of lateral hypothalamic self-stimulation was investigated. Brain stimulation reinforcement minimizes cues associated with reinforcement delivery (secondary reinforcement) and, by eliminating consummatory responses, permits precise temporal control of the interval between the operant response and reinforcement. Different groups were trained in daily 1-h sessions for brain stimulation reinforcement at one of 4 delay intervals (1, 2, 3 or 6 s). Responses made during the delay interval were not reinforced and reset the delay timer. Control groups (IMMEDIATE) were reinforced immediately, but were required to space responses--according to a delayed reinforcement of low rates (DRL) schedule--for an interval corresponding to one of the delay of reinforcement intervals. The DRL schedule equalized opportunities for reinforcement and non-reinforcement. At all intervals, rats trained with delayed reinforcement had significantly lower bar-press rates than controls trained with immediate reinforcement under DRL. When reinforcement schedules were switched (DELAY groups now get IMMEDIATE and vice versa), response rates rapidly shifted to levels appropriate to the new schedule. The pre-switch results indicate that delays even as short as 1 s markedly impede the acquisition of self-stimulation behavior. The post-switch results suggest that delay of reinforcement, like stimulation intensity, may determine the strength of hypothalamic reinforcement and hence final levels of performance.

Animals↗
PubMed1984

Does naloxone suppress self-stimulation by decreasing reward or by increasing aversion?

Fifty-eight rats were implanted with electrodes in the ventrolateral midbrain central gray from which both self-stimulation reward and/or stimulation-produced analgesia can be obtained. Thirty-nine cases were positive for self-stimulation; of these, 24 also displayed significant stimulation-produced analgesia and 15 did not. Injections of the opiate receptor blocker, naloxone, suppressed self-stimulation by approximately 40% at both analgesic and non-analgesic reward sites. Since naloxone failed to act preferentially at analgesic reward sites, the hypothesis that naloxone suppresses self-stimulation primarily by antagonizing endorphin-mediated analgesia, and thereby increasing the aversive properties of the brain stimulation, was not supported. Rather, the data are consistent with the hypothesis that naloxone suppresses self-stimulation by antagonizing endorphin-mediated reward.

Animals↗
PubMed1982

Endorphin mediation of post-ictal effects of kindled seizures in rats.

Brief electrical stimulation of the enkephalin-rich globus pallidus at 1-h intervals produced kindled, clonic seizures in rats as rapidly as similar stimulation of the amygdala. Massing the kindling trials at 10-min intervals inhibited the occurrence of subsequent seizures, especially following globus pallidus stimulation. Naloxone (20 mg/kg), an opiate receptor antagonist, reversed this post-ictal inhibition of seizures following massed trials, but had no effect on seizures kindled at 1-h intervals. Thus, endorphin-released during seizures do not appear to mediate the production of kindled seizures, but do appear to mediate the transient posts ictal inhibition of seizures.

Amygdala↗
PubMed1979

Brain endorphins: possible role in reward and memory formation.

A role for enkephalin in the mediation of behavioral reinforcement is supported by several lines of evidence: i) central injections of enkephalin serve as reinforcement for self-administration behavior, ii) electrical stimulation of many enkephalin-rich regions serves as reinforcement for self-stimulation behavior, which is blocked by moderate doses of naloxone, and iii) long-term retention of a passive avoidance response is facilitated by immediate post-learning injections of methionine-enkephalin and morphine.

Animals↗
PubMed1977

Possible role of dopamine-beta-hydroxylase in the regulation of norepinephrine biosynthesis in rat brain.

In Experiment 1, the dose-response effects of three dopamine-beta-hydroxylase (DBH) inhibitors (diethyldithiocarbamate, FLA-63 and U-14, 624) on the endogenous levels of norepinephrine and dopamine in pons-medulla of rat brain were determined. In Experiment 2, the effect of low doses of diethylithiocarbamate (2.5 to 120 mg/kg) on the level of norepinephrine-3H produced from dopamine-H3 was determined. The data obtained by extrapolation of the curves in both experiments provided an estimation of the in vivo level of DBH activity and suggested that it was not present in excess. Finally, in Experiment 3, the three DBH inhibitors reduced self-stimulation (a behavior dependent upon catecholamines) in a dose-related manner and intraventricular injections of 1-norepinephrine reinstated normal rates of self-stimulation. The results from the three experiments are consistent with the idea that DBH is involved in the regulation of norepinephrine biosynthesis. The relationship of this finding to our earlier report of a deficit of DBH in post-mortem brains of schizophrenics is discussed.

Animals↗
PubMed1977

Benzodiazepines: behavioral and neurochemical mechanisms.

The therapeutic effects of benzodiazepines in psychoneurosis may depend in part on their ability to release or disinhibit a patient's anxiety-suppressed gratification-seeking behavior. Benzodiazepines may disinhibit behavior by reducing the activity of serotonin (and possibly acetylcholine) neurons in the brain's "punishment" system. Reduction of serotonin transmission may be due to a facilitation of gamma-aminobutyric acid (GABA)-mediated presynaptic inhibition at the serotonin nerve terminal.

Acetylcholine↗