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C B Hubner

Publications and source records attributed to C B Hubner.

9 recordsLinked to original sources
PubMed1992

Heroin, 6-acetylmorphine and morphine effects on threshold for rewarding and aversive brain stimulation.

Studies investigating the reinforcing and analgesic activity of heroin and morphine have found that heroin is a more potent compound. The rapid deacetylation of heroin to 6-acetylmorphine and morphine raises questions concerning the underlying mechanism responsible for this difference in potency. The present series of experiments addressed this issue by examining, in the rat, the relative potency of heroin and its active metabolites, 6-acetylmorphine and morphine, to lower the threshold for rewarding stimulation of the medial forebrain bundle and raise the threshold for aversive stimulation of the mesencephalic reticular formation. Reward and escape thresholds were determined by using a modification of the psychophysical method of limits. Heroin was found to be approximately 40 times more potent than morphine in lowering the reward threshold and approximately 6.5 times more potent in raising the escape threshold. 6-Acetylmorphine and heroin were approximately equipotent in producing significant effects on the threshold for both rewarding and aversive brain stimulation. These findings suggest that heroin's increased potency when compared to morphine may be due, in part, to the activity of 6-acetylmorphine.

Animals↗
PubMed1991

Effects of selective D1 and D2 dopamine antagonists on cocaine self-administration in the rat.

The effect of the selective D1 antagonist, SCH 23390, and the selective D2 antagonist, spiperone, was investigated in rats trained to self-administer intravenous cocaine on a fixed-ratio (FR) 5 schedule of reinforcement. Both SCH 23390 and spiperone pretreatment increased responding up to doses of 10.0 micrograms/kg, and decreased responding at higher doses. Since rate of responding maintained by a drug can be influenced by factors other than its reinforcing efficacy, behavior maintained by cocaine was also investigated under a progressive-ratio schedule. The breaking point obtained under this schedule is used as a measure of the efficacy of the reinforcer and this value is not exclusively determined by response rate. With the progressive-ratio schedule, both SCH 23390 and spiperone produced dose-dependent decreases in the highest ratio completed in rats self-administering cocaine. The results obtained using the FR 5 and progressive-ratio schedules suggest that both D1 and D2 receptors are involved in mediating the reinforcing effects of cocaine.

Animals↗
PubMed1990

The ventral pallidum plays a role in mediating cocaine and heroin self-administration in the rat.

The hypothesis that the ventral pallidum is an important site mediating psychomotor stimulant and opiate reinforcement was tested in rats trained to self-administer i.v. cocaine or heroin. Ibotenic acid lesions of the ventral pallidum produced significant decreases in cocaine and heroin self-administration behavior maintained on a fixed-ratio 5 schedule of reinforcement, suggesting an attenuation of the reinforcing value of cocaine and heroin. On a progressive-ratio schedule, ventral pallidal lesions produced significant decreases in the highest ratio obtained in rats self-administering cocaine. Similar results were observed with heroin in a progressive-ratio procedure modified to produce higher levels of responding; lesions of the ventral pallidum produced a significant decrease in the highest ratio obtained. Further, the i.v. co-administration of naloxone and heroin produced a decrease in progressive-ratio responding relative to heroin alone using the modified progressive-ratio schedule. These results suggest that the ventral pallidum is an important site mediating the reinforcing effects of cocaine and heroin and that the nucleus accumbens-ventral pallidum circuit may be a common pathway for both stimulant and opiate reinforcement.

Animals↗
PubMed1990

Bromocriptine produces decreases in cocaine self-administration in the rat.

The effect of bromocriptine pretreatment was investigated in rats trained to self-administer intravenous cocaine on a fixed-ratio (FR) 5 schedule of reinforcement. Bromocriptine, a dopamine agonist, produced dose-dependent decreases in cocaine self-administration at doses of 4.0, 8.0, 16.0, and 32.0 mg/kg. In a separate group of rats trained on a DRL 20-second schedule of food reinforcement used to produce the same overall rate of responding for food as for cocaine on the FR 5 schedule, bromocriptine did not produce a significant effect on overall response rate, number of reinforced responses, or percent of responses that were reinforced. Given that bromocriptine produced a specific effect on cocaine-maintained responding, the present results suggest that bromocriptine is interacting with the neurochemical substrate mediating the reinforcing effects of cocaine. The potential effectiveness of bromocriptine as a pharmacotherapy for cocaine dependence is discussed.

Animals↗
PubMed1989

A role for the mesolimbic dopamine system in the psychostimulant actions of MDMA.

Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with a chemical structure that resembles both the amphetamines and mescaline and has both stimulant and perception altering properties. The stimulant properties of MDMA were assessed in photocell cages designed to measure locomotor activity in rats. MDMA, over a range of doses (2.5-10.0 mg/kg, SC) produced locomotor hyperactivity which lasted up to 4 h. Further studies examined the role of the mesolimbic dopamine system in the hyperactivity induced by MDMA. 6-Hydroxydopamine lesions of the Nucleus accumbens attenuated the locomotor response produced by MDMA. The well characterized attenuation of the locomotor response produced by amphetamine was also demonstrated in the same rats. The present study demonstrates similarities in the stimulant properties of MDMA and amphetamine, and also suggests that as with amphetamine, the locomotor activation associated with MDMA may involve the presynaptic release of dopamine in the region of the Nucleus accumbens. However, MDMA may have a more unusual pharmacological profile because of its longer duration of action, neurotoxic potential, and differences in the qualitative aspects of its psychoactive effects.

3,4-Methylenedioxyamphetamine↗
PubMed1988

The threshold lowering effects of MDMA (ecstasy) on brain-stimulation reward.

3,4-Methylenedioxymethamphetamine (MDMA) is a psychoactive phenylisopropylamine which is structurally similar to both amphetamine-related sympathomimetics and the hallucinogen, mescaline. MDMA produces pleasurable effects which include euphoria, and recent reports continue to demonstrate its widespread recreational use. The aim of the present study was to assess the effects of racemic MDMA on the threshold for rewarding intracranial self-stimulation, an animal model used to assess a drug's abuse liability in man. Rewarding electrical stimulation was delivered via electrodes stereotaxically implanted in the medial forebrain bundle-lateral hypothalamic area of the rat brain. Thresholds were determined by means of a rate-independent psychophysical method. MDMA produced a dose-related lowering of the reward threshold in all four animals tested. Given that increased sensitivity for rewarding brain stimulation, measured as a lowering of the reward threshold, is an animal model of drug-induced euphoria these results suggest a similar mode of action for its reinforcing effects as other abused substances.

3,4-Methylenedioxyamphetamine↗
PubMed1988

The reinforcing properties of the mixed agonist-antagonist buprenorphine as assessed by brain-stimulation reward.

The effect of buprenorphine on the threshold for rewarding brain stimulation to the medial forebrain bundle-lateral hypothalamus was determined in rats using a rate-independent psychophysical method. Increased sensitivity to rewarding brain stimulation (i.e., lowering of the reward threshold) was used as the measure of a drug's reinforcing action. Buprenorphine (SC) produced a significant dose-dependent lowering of the reward threshold, with effective doses varying from 0.004-0.06 mg/kg. These results are consistent with buprenorphine's euphoria producing effects in humans and its ability to sustain self-administration in animals and suggest that buprenorphine may have abuse potential.

Animals↗
PubMed1987

The combined effects of morphine and d-amphetamine on the threshold for brain stimulation reward.

The effect of morphine and d-amphetamine co-administration on the threshold for rewarding intracranial electrical stimulation was studied in rats with electrodes stereotaxically implanted in the medial forebrain bundle-lateral hypothalamic or ventral tegmental area of the brain. Thresholds were determined by means of a rate-independent psychophysical method. Individually, morphine and d-amphetamine both caused a dose-related lowering of the reward threshold. Low doses of morphine or d-amphetamine which were ineffective or minimally effective in lowering the reward threshold were then tested with various doses of either d-amphetamine or morphine, respectively. In both cases, the combined administration of morphine and d-amphetamine resulted in a lowering of the reward threshold that was greater than for the corresponding doses of morphine and d-amphetamine when given alone. Given that increased sensitivity for rewarding brain stimulation has been suggested to be an animal model of drug-induced euphoria, this effect is congruent with the reported increase in the degree of euphoria produced when amphetamine is used in conjunction with opiate drugs.

Animals↗