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Biomedical subjects

M E Olds

Publications and source records attributed to M E Olds.

At least 37 records · Page 2Linked to original sources
PubMed1984

Selective neonatal depletion of dopamine has no effect on medial prefrontal cortex self-stimulation in the rat.

The role of the dopaminergic input to the medial prefrontal cortex (MFC) on self-stimulation (SS) was investigated in adult rats injected neonatally with 6-hydroxydopamine (6-OHDA). Each subject on day 3 or 5 received bilateral intraventricular injection of 6-OHDA (total dose 200 micrograms, 50 micrograms/injection/2.5 microliters vehicle which contained 1 mg/ml ascorbic acid) or of the vehicle alone after pretreatment with desmethylimipramine (50 mg/kg i.p.) 30 min earlier. At 150 days of age, the animals were implanted with monopolar (100 microns) stainless steel electrodes in the MFC. One long (10 h) and 5 short (2 h) SS sessions resulted in similar percentages of responders for the brain reward in test and control subjects, and similar response rates in both groups. Biochemical assays of the levels of norepinephrine (NE) and dopamine (DA) in the frontal cortex showed depletion of DA 90% in the test animals, but no depletion of NE. Histochemical fluorescence visualization of the catecholamine input verified the biochemical results in the MFC. These results are viewed as negative evidence for the hypothesis that DA innervations in the MFC are critical neural substrates for SS, and suggest that activation of intrinsic neurons in the MFC are responsible for SS in the region.

Animals↗
PubMed1982

Reinforcing effects of morphine in the nucleus accumbens.

The possibility that morphine exerts in reinforcing effects via an action in the nucleus accumbens was investigated in the rat using the self-administration model and the method of intracerebral injection. Male, adult rats implanted with a chronic cannula aimed at this nucleus were tested for self-administration in a rectangular chamber equipped with two levers, one at each end. Each subject was given several sessions in blocks of two sessions for a given substance, the first session with the active lever at one end of the chamber, the next with the active lever at the other end. During a session, responses on the inactive lever were without consequences. Depression of the active lever was coupled with the presentation of a tone to facilitate discrimination between the two levers. All subjects received a sequence of 5 sessions, the first for habituation, the next two to test for effects of artificial cerebrospinal fluid, and the next two to test for effects of morphine. A few subjects in which the cannula had not been dislodged or plugged were further tested for effects of morphine and then for effects of morphine mixed with naloxone. Each response on the active lever resulted in an injection of 0.02 microliter. During the morphine sessions, this volume contained 0.2 microgram of the opiate; during the sessions of morphine and naloxone, this volume contained 0.2 microgram morphine mixed with 0.2 microgram naloxone. The results show that self-administration was induced and maintained when morphine was injected inside the nucleus accumbens, not in an area outside this region but at the same brain level. The rate or responding on the active lever for morphine was higher than for artificial cerebrospinal fluid and it showed a pattern of gradual increase over time. In contrast, the rate of responding on the inactive lever during the morphine sessions showed a decline. This pattern was not evident in these animals during control sessions and in the animals in which the injections were outside the n. accumbens. These results are interpreted to indicate that the n. accumbens may be part of a system of structures mediating the reinforcing effects of opiates.

Animals↗
PubMed1981

Presynaptic alpha-adrenergic mediation of self-stimulation in locus coeruleus in rats treated neonatally with 6-hydroxydopamine.

Rats self-stimulating in the region of the locus coeruleus and treated neonatally with 6-hydroxydopamine (6-OHDA) injected bilaterally in the same region were tested for effects of adrenergic receptor blockers on a lever-pressing behavior to obtain the brain reward. The neonatally treated animals (16 microgram total dose, 8 microgram X 2) self-stimulated at abnormally high rates compared with controls. Yohimbine (5 mg/kg i.p.) and phentolamine (5 mg/kg) suppressed self-stimulation in controls and treated subjects. Phenoxybenzamine (10 mg/kg) reduced the response rate for the brain reward but did not abolish the behavior in the 6-OHDA-treated animals and had minor effects in controls. Propranolol (10 mg/kg) had no effects. The 6-OHDA subjects tested for the effects of D-amphetamine and L-amphetamine (0.5 mg/kg) showed facilitation of responding after the former but not after the latter. Self-stimulation in the 6-OHDA subjects was suppressed by treatment with alpha-methyl-p-tyrosine and pimozide. The significance of these findings is discussed in terms of the use of alpha-adrenoreceptor antagonists to separate the pre- from the post-synaptic action of released norepinephrine and in terms of the norepinephrine hypothesis of rewarding effects of brain stimulation in the dorsal pons.

Animals↗
PubMed1981

Effects of neonatal 6-hydroxydopamine treatment on catecholamine levels and behavior during development and adulthood.

The effects of neonatal intraventricular 6-hydroxydopamine (6-OHDA) (50-400 microgram) treatment on catecholamine levels in various brain regions, and on motor activity, were investigated in rats during development and adulthood. At 30 days catecholamine levels were lower in the frontal cortex and ventral diencephalon; minor reductions were observed in midbrain and pontine regions. At 90 days the effects of 6-OHDA treatment were similar in frontal and rostral midbrain regions but in the pontine area norepinephrine levels were substantially elevated. Behavioral tests in a stabilimeter indicated 6-OHDA-treated rats were hyperactive during development, at 25 and 35 days of age, as well as in adulthood. However, 6-OHDA-treated rats did not differ from controls in habituation. These effects are interpreted as supporting the notion that low catecholamine levels in the forebrain alter activity during development and in adulthood.

Aging↗
PubMed1981

Catecholamine-serotonin interaction effects on activity in rats neonatally treated with 6-hydroxydopamine.

The effect of increased central serotonergic levels on motor activity was investigated in rats neonatally treated with 6-hydroxydopamine (6-OHDA) in the lateral ventricles. Regional brain assays of monoamine levels in 90-day-old rats showed depletion of catecholamines, but not of serotonin, in the forebrain accompanied by a large elevation of norepinephrine, and minor elevation of serotonin, in the hindbrain. Measures of behavioral activity in adulthood were taken after treatment with saline, pargyline, L-tryptophan, or pargyline given 30 min before L-tryptophan. The combined treatment of pargyline plus L-tryptophan produced hyperactivity in controls and this effect was blocked in the 6-OHDA-treated animals. These findings indicate that the serotonergic system is capable of influencing motor activity, but that this influence is blocked in animals permanently depleted of catecholamines in their terminal field regions.

Animals↗
PubMed1981

Activity responses to morphine and amphetamine in rats with elevated NE levels in the pons.

The catecholaminergic basis of the stimulant actions of amphetamine and morphine was investigated in adult rats treated neonatally with 6-hydroxydopamine (6-OHDA) to produce depletion of cortical catecholamines and marked elevation of norepinephrine in the pons. On days 3, 5, 7 and 9 after birth, rat pups were injected bilaterally in the lateral ventricles with 100, 200, or 400 micrograms of 6-OHDA, dissolved in artificial cerebrospinal fluid (CSF). A control group was injected with the CSF vehicle. The capacity of amphetamine (2 mg/kg) and morphine (1.25, 2.5, and 3.5 mg/kg) to produce behavioral stimulant effects was then subsequently tested in adults. The stimulant effect of amphetamine was attenuated in animals pretreated with 100 and 200 micrograms 6-OHDA and was blocked in those treated with 400 micrograms 6-OHDA. The stimulant effects obtained with morphine were blocked by all 6-OHDA doses (100 and 200 micrograms). For morphine, no tests were made in the 400 micrograms 6-OHDA group on the basis of results obtained in animals pretreated with the lower doses of 6-OHDA. These results are discussed in terms of differing roles played by the catecholamine systems in the production of behavioral stimulation.

Amphetamine↗
PubMed1980

Self-administration of D-Ala2-Met-enkephalinamide at hypothalamic self-stimulation sites.

The relationship between the action of enkephalin and the reinforcing action of electrical stimulation in the posterior lateral hypothalamus of the rat was studied with the self-administration approach. Adult male albino rats implanted with a combination cannula and stimulation electrode in hypothalamus were pretested for the reinforcing effects of electrical stimulation. Only subjects that self-stimulated at moderate to high rates were given self-administration tests. The chamber for the self-administration tests was fitted with one lever at each end of a rectangular plexiglass box. In a session, one lever was 'active', the other not. The active lever, if depressed, yielded 20 nl of CSF (artificial cerebrospinal fluid), or CSF in which one of the test substances was dissolved. Each subject was tested repeatedly for the reinforcing effects first of a control solution (CSF), then of D-Ala2-Met-enkephalin (DALA), a long-acting synthetic analogue of enkephalin, then of morphine, and then of opioids mixed with naltrexone or naloxone. Following these tests, the subjects were once again given self-stimulation tests to ascertain the functional integrity of the 'reward' system after the repeated self-administration tests. The results demonstrate that when the test solution was DALA instead of CSF the subjects pressed the active lever at a higher rate than for CSF, and they exhausted the supply more rapidly than for CSF. The rate on the active lever was also significantly higher than on the inactive lever. DALA at 1 and 5 microgram/microliter concentrations proved more reinforcing than at 0.1 microgram/microliter. Naltrexone did not block the reinforcing effect of DALA, whereas naloxone blocked DALA-induced reinforcement. These data extend the report of ventricular methionine-enkephalin positive reinforcement to DALA injected directly into the lateral hypothalamus.

Animals↗
PubMed1979

Peripheral auditory input to the midbrain limbic area and related structures.

The effect of peripherally applied auditory stimulation on unit activity in midbrain limbic and related regions was investigated in the freely behaving rat. Two pure tones (1 and 10 kHz) and a noise generated by the discharge of a solenoid were used as stimuli presented randomly with 1 min mean interval between presentations. Computer-aided analysis of unit activity indicated that (1) a high proportion of neurons in the limbic midbrain region give excitatory responses to the three stimuli; (2) a majority of the responses have short latencies, especially in the dorsal raphe nucleus; (3) frequency and physical properties of the stimuli seemed not crucial for eliciting responsiveness; (4) habituation to repeated presentation of stimuli was not characteristic of the excitatory responses in the limbic midbrain region. These results are discussed in the light of possible functions of this region.

Acoustic Stimulation↗
PubMed1975

Effects of intraventricular 6-hydroxydopamine and replacement therapy with norepinephrine, dopamine, and serotonin on self-stimulation in diencephalic and mesencephalic regions in the rat.

Although 6-hydroxydopamine (6-OHDA) reduced the rate of hypothalamic self-stimulation, it is not known whether the same effect is produced at other reinforcing sites remote from the hypothalamus. This was investigated in rats implanted with rewarding probes in the hypothalamus, in the substantia nigra, in the midbrain, and in the pontine region. Two patterns of self-stimulation emerged in each subject. One, characterized by short, medium and long-stimulus-train durations, was seen in the hypothalamus, in the substantia nigra, and in selected sites in the pons. The other, which comprised only short stimulus-trains, was found in the medial midbrain and in the pontine region. 6-OHDA (250 mug intraventricular route) reduced the rate of responding in the regions where responding was for short, medium, and long stimulus trains. It has a minor effect on responding in regions where the brain rewards were exclusively of short duration. Thus, self-stimulation in the hypothalamus, in the substantia nigra and in the pons was suppressed after 6-OHDA, while self-stimulation in the medial midbrain and at sites in the pons, where selection was for short trains, was only slightly below control levels after 6-OHDA. L-Norepinephrine (L-NE) (10, 20 and 30 mug) injected into the lateral ventricle of the 6-OHDA-treated rats temporarily reinstated self-stimulation in the lateral hypothalamus but not in the substantia nigra and not in the pontine region where the pattern of selection had been for long brain rewards. Dopamine (DA) was not effective as an antagonist of the suppressant action of 6-OHDA. Serotonin (5-HT) reinstated self-stimulation behavior in the lateral hypothalamus but not in the other positive regions. Its action was less than that of NE and did not take place in all animals tested.

Animals↗