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S D Iversen

Publications and source records attributed to S D Iversen.

At least 91 records · Page 5Linked to original sources
PubMed1989

Blockade of apomorphine-induced yawning in rats by the dopamine autoreceptor antagonist (+)-AJ 76.

The effects of the putative, selective dopamine autoreceptor antagonist (+)-AJ 76 on yawning, penile grooming and mouth movements induced by small doses of apomorphine in male rats were examined. Yawning induced by 0.05mg/kg apomorphine was dose dependently blocked by (+)-AJ-76, significant decreases being observed at 0.86 and 3.5mg/kg of the drug. A dose of 0.86mg/kg (+)-AJ 76 caused a two fold shift to the right of the apomorphine dose response curve for yawning. In contrast, (+)-AJ 76 had no effect on penile grooming and vacuous mouth movements induced by small doses of apomorphine. This pattern of results is similar to that observed after bilateral 6-hydroxydopamine-induced lesions of the substantia nigra which also blocked apomorphine-induced yawning but spared penile grooming and mouth movements. Previous studies have suggested that (+)-AJ 76 is a selective dopamine autoreceptor antagonist that has little or no effect on behaviour mediated by post-synaptic dopamine receptors. Therefore, these data provide further support for the hypothesis that apomorphine-induced yawning is mediated by dopamine autoreceptors.

Animals↗
PubMed1989

Morphine-induced analgesia in the rat paw pressure test is blocked by CCK and enhanced by the CCK antagonist MK-329.

The effects of cholecystokinin octapeptide sulphated (CCK) and the potent CCK antagonist MK-329 (L-364, 718) on analgesia induced by morphine in the paw pressure test in the rat were examined. Both CCK (4-16 micrograms/kg) and MK-329 (0.1-8.0 mg/kg) had no significant effect on thresholds for pain when given alone, whereas morphine (2-16 mg/kg) induced dose-dependent analgesia. Cholecystokinin (4-16 micrograms/kg) abolished the analgesia induced by 8 mg/kg morphine. In contrast, doses of 1 and 2 mg/kg MK-329 enhanced the analgesia induced by 8 and 4 mg/kg morphine, respectively. The present data are consistent with previous reports that CCK blocks, and CCK antagonists enhance, opiate-induced analgesia in response to thermal pain stimuli. In addition, the results show that CCK/opiate interactions extend to mechanical pain stimuli. Recent ligand binding studies have shown that CCK receptors in the spinal cord of the rat (where CCK/opiate interactions are thought to occur) are predominantly of the CCK-B subtype. The drug MK-329 has a relatively weak (micromolar) affinity for CCK-B receptors and a high affinity (nanomolar) for CCK-A receptors. As relatively large doses (1-2 mg/kg) of MK-329 are required to enhance opiate-induced analgesia in the paw pressure test and tail flick test in rats it appears that CCK/opiate interactions in this species involve CCK-B receptors.

Animals↗
PubMed1989

Day and night locomotor activity effects during administration of (+)-amphetamine.

Rats were given continuous subcutaneous amphetamine infusions (0, 2, 6, 10 and 20 mg/kg/day) via osmotic minipumps. The effects of these treatments on the locomotor activity of rats were determined over both light and dark phases of a 12-hr light/dark cycle for 336 consecutive hours. It was observed that tolerance to the locomotor stimulant actions of (+)-amphetamine is both dose- and light/dark cycle-dependent. Locomotor stimulation induced by the two highest doses remained high during both day and night throughout the period of treatment, except for the first few days and nights with the highest dose. Tolerance developed only to the effects of the two lower doses, and only during the day. Effects of the low doses on locomotor activity and on circadian patterns of locomotor activity are roughly similar to those previously observed with continuous administration of a selective dopamine D2 agonist. This behavioral similarity suggests that dopamine released by continuous administration of low doses of (+)-amphetamine may be producing its effects via selective actions on DA D2 receptors in vivo.

Amphetamines↗
PubMed1989

Functional compensation afforded by grafts of foetal neurones.

1. Adult neurones grafted to the adult nervous system show limited survival and growth potential. By contrast, certain foetal neurones of a defined age, when grafted to the damaged adult nervous system survive, and form a dense innervation of the host brain with morphologically defined synapses. Monamine containing neurones in the rat have these properties. In a number of model systems their ability to survive grafting to the adult brain has been demonstrated, the optimal conditions for their survival and the importance of endogenous growth factors continue to be investigated. 2. Lesions of the ascending dopamine pathways to the dorsal and ventral striatum result in profound motor disorders. Dopamine-rich foetal neurones from the mesencephalon grafted as blocks of tissue or as cell suspensions provide a rich innervation to the dopamine-depleted target areas and reverse many of these motor impairments. Similar models have been developed for the cholinergic innervation from the basal forebrain to the hippocampus and cortex. Cholinergic depletion of these forebrain structures impair performance on spatial memory tasks, which are reversed by grafts of foetal basal forebrain neurones to cortex or hippocampus. 3. The grafting model is a powerful tool with which to define the functional role of neurotransmitters in brain function. The neurological properties of foetal monoamine and cholinergic neurones which underlie their ability to afford functional compensation to the damaged nervous system and their vulnerability in certain degenerative diseases of the CNS in man remain obscure.

Animals↗
PubMed1989

Antiparkinsonian efficacy of a novel transdermal delivery system for (+)-PHNO in MPTP-treated squirrel monkeys.

We examined the ability of the antiparkinsonian agent (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) to enter the systemic circulation in therapeutic concentrations after continuous transdermal absorption in squirrel monkeys rendered parkinsonian by MPTP. Direct subcutaneous administration of (+)-PHNO in the dose range of 2.5 to 20 micrograms/kg restored locomotor activity to levels seen in normal monkeys for approximately 1 hour. Application of transdermal patches capable of delivering, into an infinite sink, an estimated 2.6 micrograms/cm2/h of (+)-PHNO over a skin surface area of 4.78 to 19.12 cm2 also restored locomotor activity to the normal range during a 24-hour period. We suggest the use of transdermal application of PHNO as a novel drug delivery system for the improved management of Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1989

NB-355: a novel prodrug for L-DOPA with reduced risk for peak-dose dyskinesias in MPTP-treated squirrel monkeys.

Prodrugs may be used to improve the absorption and bioavailability of certain active compounds. We have examined the ability of a novel catechol monoester of L-DOPA, NB-355 [L-3-(3-hydroxy-4-pivaloxyloyphenyl)alanine], to stimulate locomotor activity and induce dyskinesias in MPTP-treated primates. In the presence of carbidopa, a dose-dependent increase in locomotor activity over 4 1/2 h was observed following administration of L-DOPA (10, 20 or 40 mg/kg p.o.) or NB-355 (20, 40 or 80 mg/kg p.o. dopa equivalent). The dose-response curve for NB-355 was shifted to the right such that approximately twice the dopa equivalent dose of NB-355 was required to stimulate locomotor activity to the same level observed for L-DOPA. At doses matched for total locomotor stimulation over the 4 1/2-h period (20 mg/kg L-DOPA and 40 mg/kg NB-355), there was a more gradual rise and increase in the duration of motor stimulation by approximately 40% using NB-355. At these doses, drug-induced dyskinesias were less severe following treatment with NB-355 than with L-DOPA. Our findings suggest that NB-355 may be a useful therapeutic agent for increasing the duration of action of L-DOPA and reducing the severity of peak-dose dyskinesia.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Transplantation of embryonic ventral forebrain grafts to the neocortex of rats with bilateral lesions of nucleus basalis magnocellularis ameliorates a lesion-induced deficit in spatial memory.

Embryonic ventral forebrain grafts containing developing cholinergic cells were transplanted to the neocortex of rats with bilateral quisqualic acid lesions of the nucleus basalis magnocellularis. A lesion-induced deficit on performance of a spatial alternation test of memory was reduced by such transplants. When the same animals were treated with the acetylcholinesterase inhibitor physostigmine (0.05 mg/kg), however, performance on the behavioral task was not further promoted, and therefore, under these conditions, the cholinergic cortical transplants appear not to be subject to modulation by anticholinesterase drugs.

Acetylcholinesterase↗
PubMed1988

Long-term motor stimulant effects of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO), a dopamine D-2 receptor agonist: interactions with a dopamine D-1 receptor antagonist and agonist.

Rats were given continuous infusions of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, 5 micrograms/h), a dopamine D-2 receptor agonist, using subcutaneous implants of ALZET osmotic minipumps. It was observed that tolerance occurred to the motor stimulant effects of PHNO during the light cycle of each day, but not during the dark cycle. Rather, the motor stimulant actions of PHNO were gradually augmented during successive nights. Daytime tolerance to the stimulant actions of PHNO was reversed by a mild environmental stress or by administration of the D-1 receptor agonist, SKF 38393 (6 mg/kg i.p.). Co-administration of the dopamine D-1 receptor antagonist, (SCH 23390, 20 micrograms/h s.c. by ALZET osmotic minipumps), initially blocked the motor stimulant actions of PHNO and also attenuated the reversal of tolerance to PHNO produced by stress, without blocking the actions of stress on activity in vehicle-infused animals. These results indicate that tolerance to the behavioural effects of PHNO may result from a loss of activation of D-1 receptors by endogenous DA.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Enhancement of morphine analgesia and prevention of morphine tolerance in the rat by the cholecystokinin antagonist L-364,718.

The potent and selective non-peptide cholecystokinin (CCK) antagonist L-364,718 (0.5-2.0 mg/kg s.c.) enhanced the analgesia induced by acute morphine treatment in the rat tail flick test. Chronic treatment with L-364,718 (1.0 mg/kg) prevented the development of tolerance to morphine analgesia (after a 6 day period of morphine treatment) but did not influence the onset of opioid dependence. Since L-364,718 is considerably more potent in inhibiting CCK binding to peripheral tissues than to brain membranes its interaction with morphine is surprising. The exact locus of this interaction, or whether it involves 'peripheral-type' (CCK-A) or 'central-type' (CCK-B) receptors is not known.

Analgesia↗
PubMed1988

The NK-3 tachykinin agonist senktide elicits yawning and chewing mouth movements following subcutaneous administration in the rat. Evidence for cholinergic mediation.

The selective NK-3 tachykinin receptor agonist senktide elicited yawning, chewing mouth movements and sexual arousal following subcutaneous administration (0.1-1.0 mg/kg) in the rat. These responses were not significantly affected by the dopamine antagonist haloperidol (0.03 mg/kg) or by 6-hydroxydopamine lesions of the nigrostriatal projection. In contrast, the behaviours were markedly attenuated by the peripheral and central muscarinic antagonist scopolamine (1 mg/kg), but not by the peripheral muscarinic antagonist N-methylscopolamine (1 mg/kg). These findings suggest that stimulation of NK-3 receptors produces yawning, chewing and sexual arousal by directly activating central cholinergic neurons.

Animals↗
PubMed1988

Chronic administration of a selective dopamine D-2 agonist: factors determining behavioral tolerance and sensitization.

The locomotor stimulant effects of sustained administration of a potent and selective dopamine (DA) D-2 receptor agonist, [+]-4-propyl-9-hydroxynaphthoxazine (PHNO), in rats were assessed 24 h a day during 12 h light-dark cycles. PHNO was administered continuously with subcutaneous implants of Alzet osmotic minipumps (5 micrograms/h), for 12 h a day with modified osmotic minipumps (5 micrograms/h), or by daily injections (15 micrograms, SC). Tolerance was observed to occur only with 24 h continuous infusions and only during the light period. The other treatment regimens produced sensitization of the locomotor response. Daytime tolerance to continuous infusions of PHNO was reversed following reversal of the light-dark cycle. A normally 'arousing' stimulus also reversed (temporarily) daytime tolerance. The present results indicate that the temporal pattern of administration of DA agonists, the phase of the circadian cycle and environmental stimuli associated with arousal are important determinants of the behavioral consequences of long-term treatment.

Animals↗
PubMed1988

8-OH-DPAT elicits feeding and not chewing: evidence from liquid diet studies and a diet choice test.

There have been recent claims that the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits chewing and eating of solid but not liquid foods. Therefore, the effects of 8-OH-DPAT and another 5-HT1A agonist gepirone on the consumption of a liquid chow diet, by free feeding male rats, were examined. Both drugs produced a dose-dependent increase in the consumption of liquid diet during a 2 h test. The doses of 8-OH-DPAT and gepirone which increased liquid diet intake in this study were in the same range as those which were found previously to increase food pellet consumption by free feeding rats. The effects of 8-OH-DPAT were also examined in a feeding choice test in which free feeding animals were allowed to choose between food pellets and a liquid chow diet. In this test, 8-OH-DPAT significantly increased total food intake (liquid plus pellet) but had no significant effect on the consumption of either liquid or pellet diets when analysed separately. Thus, there were large individual differences in diet choice after 8-OH-DPAT injection. However, rats did not consistently choose to eat food pellets rather than the liquid diet, as would be predicted if the drug elicited chewing rather than eating. These results provide strong evidence that 8-OH-DPAT elicits a behaviourally specific hyperphagia and not chewing or gnawing.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Delay-dependent short-term memory deficits in aged rats.

Separate groups of rats of three ages (6 month, 15 month or 24 month) were trained in a two-lever operant chamber on one of two versions of a paired-trial delayed response task involving either matching or non-matching of the choice response to a sample lever. The older rats were unimpaired in learning either version of the task during initial training with no (0 s) delay between the sample and choice responses. However, when variable 0-24 s delay intervals were introduced, the 24-month group was impaired on acquisition of the delayed non-matching task, and both the 15- and 24-month groups were impaired on acquisition of the delayed matching task compared to the 6-month group. Deficits in the older groups in asymptotic performance were attributable to an impairment at longer delay intervals whilst maintaining near perfect performance at the shorter delay intervals, suggesting a selective short-term memory impairment. The delay-dependent deficits of the older groups were not ameliorated by the muscarinic agonist arecoline or the cholinesterase inhibitor physostigmine, and so failed to corroborate a cholinergic interpretation of the observed age-related impairment in short-term memory.

Aging↗
PubMed1988

The 5-HT1A agonist 8-OH-DPAT increases consumption of palatable wet mash and liquid diets in the rat.

The 5-HT1A agonist 8-OH-DPAT, at a dose of 30 micrograms/kg, enhanced the consumption of sweetened wet mash and sweetened milk in non-deprived rats. In partially satiated rats, sensitivity to the hyperphagic effect of 8-OH-DPAT on wet mash intake was substantially increased, so that the minimally effective dose was reduced to 3 micrograms/kg. Similarly, 8-OH-DPAT was more efficacious in increasing milk intake in satiated rats. Thus, 30 and 40 micrograms/kg 8-OH-DPAT produced a 4-fold increase of milk intake in completely satiated rats compared to a 2-fold increase in partially satiated animals at a dose of 30 micrograms/kg. The increased intake of liquid and wet mash diets observed after treatment with low doses of 8-OH-DPAT argues against the involvement of non-specific gnawing in the increased consumption of solid food produced by the drug. Rather, the data suggest that 8-OH-DPAT may specifically stimulate appetite by counteracting a tonic serotonergic inhibition of feeding. The present experiments also showed that 8-OH-DPAT attenuates fenfluramine-induced anorexia which is thought to depend on increased serotonergic neurotransmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1988

Cholinergic grafts in the neocortex or hippocampus of aged rats: reduction of delay-dependent deficits in the delayed non-matching to position task.

Aged (24 month) rats have previously been shown to manifest delay-dependent deficits in the performance of an operant delayed non-matching to position task. In the present experiment, cholinergic-rich grafts implanted into either the neocortex or the hippocampus of aged rats are shown to reinnervate the host neocortex and hippocampus, respectively, and to provide a significant amelioration of the host animals' short-term memory impairments. The results are discussed in light of the cholinergic hypothesis of geriatric memory dysfunction.

Aging↗
PubMed1988

Place navigation in rats is impaired by lesions of medial septum and diagonal band but not nucleus basalis magnocellularis.

The role of forebrain cholinergic projections in place navigation learning was assessed in two experiments. Following surgery, rats were required to learn the spatial location of an underwater platform on the basis of distal room cues. Bilateral injections of ibotenic acid into the nucleus basalis magnocellularis depleted choline acetyltransferase (ChAT) from the anterior and temporoparietal cortex but not the hippocampus. Separate histological studies confirmed the accuracy of the lesions and demonstrated a marked loss of cortical acetylcholinesterase. These rats subsequently showed no deficits in spatial learning or memory. In a second experiment, bilateral lesions of the vertical limb of the diagonal band of Broca and medial septum depleted ChAT from the hippocampus and posterior cortex but not the anterior cortex. Histological studies confirmed the accuracy of the lesion and showed a pronounced loss of acetylcholinesterase from the hippocampus. These rats were deficient in spatial learning and showed reduced spatial bias during transfer tests. The data are discussed in the light of the hypothesis that the cholinergic innervation of the hippocampus plays a key role in spatial reference memory processes involved in place navigation.

Animals↗
PubMed1988

The NK-3 tachykinin receptor agonist senktide elicits 5-HT-mediated behaviour following central or peripheral administration in mice and rats.

The behavioural effects of the selective NK-3 tachykinin receptor agonist senktide were studied following intracisternal and subcutaneous administration in rodents. Behavioural manifestations of 5-hydroxytryptaminergic stimulation, including head twitches (mice), wet dog shakes (rats), forepaw treading, flat body posture, hindlimb splaying and Straub tail, were seen following the intracisternal (0.01-1.2 nmol) or subcutaneous (0.1-2.4 mumol kg-1) administration of senktide in both species. We conclude that stimulation of NK-3 receptors stimulates 5-hydroxytryptaminergic pathways in rodent brain, and that senktide may cross the blood-brain barrier in biologically significant amounts.

Animals↗