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PubMedDate not supplied

[Interaction of sydnocarb with preparations influencing the metabolism of catecholamines].

Changes in the stimulating action of sydnocarbum and d,1-amphetamine on the locomotor activity of mice and conditioned reflexes of rats following introduction of reserpine, alpha-methyl-para-tyrosine (alpha-Mt) and nialamide were studied. The stimulating effect of sydnocarbum is in a great measure suppressed by reserpine, while that of amphetamine--by alpha-MT. Nialamide potentiates the stimulating action of both agents, the strengthening of the sydnocarbum effect, however, was more marked than that of amphetamine. The noted difference in the action of sydnocarbum and amphetamine was, possibly, due to the influence of the former chiefly on the stable, and of the second--on the labile neuronal norepinephrine depot.

Amphetamine↗

PubMed1994

Transmission in a locomotor-related group Ib pathway from hindlimb extensor muscles in the cat.

It has been previously shown that phasic stimulation of group I afferents from ankle and knee extensor muscles may entrain and/or reset the intrinsic locomotor rhythm; these afferents are thus acting on motoneurones through the spinal rhythm generators. It was also concluded that the major part of these effects originates from Golgi tendon organ Ib afferents. Transmission in this pathway to lumbar motoneurones has now been investigated during fictive locomotion in spinal cats injected with nialamide and L-DOPA, and in decerebrate cats with stimulation of the mesencephalic locomotor region. In spinal cats injected with nialamide and L-DOPA, it was possible to evoke long-latency, long-lasting reflexes upon stimulation of high threshold afferents before spontaneous fictive locomotion commenced. During that period, stimulation of ankle and knee extensor group I afferents evoked oligosynaptic excitation of extensor motoneurones, rather than the "classical" Ib inhibition. Furthermore, a premotoneuronal convergence (spatial facilitation) between this group I excitation and the crossed extensor reflex was established. During fictive locomotion, in both preparations, the transmissions in these groups I pathway was phasically modulated within the step cycle. During the flexor phase, the group I input cut the depolarised (active) phase in flexor motoneurones and evoked EPSPs in extensor motoneurones; during the extensor phase the group I input evoked smaller EPSPs in extensor motoneurones and had virtually no effect on flexor motoneurones. The above results suggest that the group I input from extensor muscles is transmitted through the spinal rhythm generator and more particularly, through the extensor "half-centre". The locomotor-related group I excitation had a central latency of 3.5-4.0 ms. The excitation from ankle extensors to ankle extensors remained after a spinal transection at the caudal part of L6 segment; the interneurones must therefore be located in the L7 and S1 spinal segments. Candidate interneurones for mediating these actions were recorded extracellularly in lamina VII of the 7th lumbar segment. Responses to different peripheral nerve stimulation (high threshold afferents and group I afferents bilaterally) were in concordance with the convergence studies in motoneurones. The interneurones were rhythmically active in the appropriate phases of the fictive locomotor cycle, as predicted by their response patterns. The synaptic input to, and the projection of these candidate interneurones must be fully identified before their possible role as components of the spinal locomotor network can be evaluated.

Animals↗

PubMedDate not supplied

Pharmaco-histochemical studies on a specific monoamine in the gustatory epithelia of the rabbit.

The foliate, vallate and fungiform papillae of the rabbit's tongue were studied fluorescence-histochemically under normal and experimental conditions. In normal animals a yellow fluorescence suggesting the presence of a serotonin-like monoamine was demonstrated only in taste bud cells of the foliate papilla, though its intensity was very weak. The fluorescence disappeared completely following reserpine treatment, while it was significantly enhanced by the treatment with nialamide. The fluorescence of taste bud cells could be clearly distinguished from that of catecholamines by the treatment with alpha-MMT followed by nialamide. When 5-HTP, 5-HT and 5,6-DHT were administered separately, each of these drugs was selectively taken up in taste bud cells of the foliate and vallate papillae, but no fluorescent cells were observed in the fungiform papilla. From the present results, it seems reasonable to conclude that the fluorigenic amine of taste bud cells may be 5-HT (serotonin), or at least an indoleamine derivative. Also, it is suggested that the taste bud of the vallate papilla contains a cell type which can potentially synthesize a biogenic amine in situ, or is actually synthesizing it in a very small amount just like in the case of the taste bud of the foliate one.

Animals↗

PubMed1992

Evaluation of central adrenergic receptor signal transmissions after an antidepressant administration to the rat.

The effects of several antidepressants, amitriptyline, citalopram, desipramine, fluoxetine, maprotiline, mianserin, nialamide, nomifensine, tranylcypromine and viloxazine, on the accumulation of cyclic AMP and inositol monophosphates were studied in rat cerebral cortical slices. The two enzymatic systems were stimulated either by adrenergic agonists or by forskolin. Cyclic AMP and inositol monophosphates (IPs) formed were determined by a double label method. In vitro all drugs, except inhibitors of monoamine oxidase, nialamide and tranylcypromine, inhibited alpha 1-agonist-mediated production but did not modify the cyclic AMP accumulation. Otherwise, chronic desipramine but not citalopram administration decreased the accumulation of cyclic AMP (-39%) elicited by beta-adrenoceptor agonists; no change was observed in inositol phosphate metabolism after administration of these two drugs. These data support previous investigations showing a decrease in cyclic AMP production after chronic treatment with norepinephrine uptake blockers but do not confirm the hypothesis of a modification of alpha 1-adrenoceptor-stimulated inositol phosphate metabolism.

Animals↗

PubMed1975

Effect of ergot drugs on central 5-hydroxytryptamine neurons: evidence for 5-hydroxytryptamine release or 5-hydroxytryptamine receptor stimulation.

In combined biochemical and functional studies it has been possible to show that ergocornine (0.5-5 mg/kg) and the ergolene derivative (5R,8R)-8-(4-p-methoxyphenyl-1-piperazinylmethyl)-6-methylergolene (PTR 17402; MPME) (0.25-5 mg/kg) reduce in a dose-dependent way brain 5-hydroxytryptamine (5-HT) turnover in rat as evaluated with the tryptophan hydroxylase inhibitor, alpha-propyl-dopacetamide (H 22/54), whereas 2-Br-alpha-ergocryptine (CB 154; Br-EC) had no effect on brain 5-HT turnover. Effects on 5-HT receptor activity were evaluated using the extensor hindlimb reflex of acutely spinalized rats. It was found that ergocornine increased the 5-HT receptor activity independent of presynaptic 5-HT stores and that it didnot have any effects on uptake, retention and spontaneous overflow of 3-H-5-HT in vitro but reduced the fiedl stimulation-induced release of 3-H-5-HT in vitro. Therefore, it is suggested that ergocornine is a 5-HT recpetor-stimulating agent, an effect which may lead to reduction of nervous impulse flow in the 5-HT neurons and subsequently of 5-HT release and turnover. MPME, on the other hand, seems to increase 5-HT receptor release of 5-HT stores, mainly from extragranular sites. Thus, the increase in extensor reflex activity found after MPME was reduced by reserpine and H 22/54 and enhanced by nialamide and in vitro MPME markedly increased 3-H-5-HT overflow in cortical slices of nialamide-pretreated rats and inhibited uptake and retention of 3-H-5-HT (EC50 equals 1.6 times 10-minus 6 M) in cortical slices of normal rats. Inhibition of the 5-HT membrane pump does not seem to be of any major importance, since chlorimipramine was only weakly active on the extensor reflex in the pharmacological models used and since MPME did not block but rather enhanced the 5-HT depletion caused by 4-methyl-alpha-ethyl-m-tyramine. It is suggested that MPME is a releaser of extragranular 5-HT stores leading to increased 5-HT receptor activity and reduction of 5-HT turnover in the same way as indicated for ergocornine. This new ergolene derivative may represent a new class of antidepressant drugs acting via release of extragranular 5-HT stores.

Animals↗

PubMed1985

Actions and interactions of benzodiazepine agonists, antagonists and inverse agonists on suprahyoid muscle twitching.

Amphetamine-induced twitching of the suprahyoid muscle in nialamide-pretreated, urethane-anaesthetised rats was inhibited by the benzodiazepine agonists RU 32007, diazepam and chlordiazepoxide and the GABAA agonist muscimol. Ro15-1788 and CGS 8216 induced slight, or no reduction in twitching, respectively, but reversed the effect of RU 32007 and diazepam. Ro15-1788 did not reverse the effect of muscimol. Picrotoxin reversed both muscimol and RU 32007 effects at a dose which induced only a small increase in twitching alone. Higher doses of picrotoxin markedly increased amphetamine twitching and induced twitching in the absence of amphetamine. Ethyl-beta-carboline-3-carboxylate (BCE) weakly increased twitching and reversed the effect of RU 32007. CL 218872 weakly reduced twitching but also weakly antagonised RU 32007. In rats pretreated with a higher dose of nialamide methyl beta-carboline-3-carboxylate (BCM) and BCE induced twitching. BCE-induced twitching was antagonised by RU 32007, Ro15-1788, CGS 8216, muscimol and weakly by CL 218872. Thus, benzodiazepine agonists inhibit twitching and inverse agonists induce twitching, both being blocked by antagonists. Partial agonism (CL 218872) or partial inverse agonism (CGS 8216) may be detected by differential effects against different inducers of twitching.

Amphetamine↗

PubMed1988

5-Hydroxytryptamine-immunoreactive neurons and nerve fibers in the superior cervical ganglion of the rat.

Indirect immunofluorescence method was used to localize 5-hydroxytryptamine-immunoreactive structures in the superior cervical ganglion of adult rats. In the ganglia of normal rats, 5-hydroxytryptamine immunoreactivity was localized in the small intensely fluorescent cells, but not in principal nerve cells. In the superior cervical ganglion of rats, pretreated with nialamide, a monoamine oxidase inhibitor, 150 mg/kg i.p., and the 5-hydroxytryptamine precursor, L-tryptophan, 45 mg/kg i.p., a large number of 5-hydroxytryptamine-immunoreactive principal nerve cells and small intensely fluorescent cells were detected. The immunoreactive principal nerve cells had long processes, and 5-hydroxytryptamine-immunoreactive nerve fibers were observed traversing the ganglion. In ganglia of rats pretreated with colchicine, occasional 5-hydroxytryptamine-immunoreactive principal nerve cells and several small intensely fluorescent cells were detected. Ligation of the main postganglionic nerve trunks of the superior cervical ganglion of normal rats resulted in the appearance of several 5-hydroxytryptamine-immunoreactive principal nerve cells and nerve fibers in the ganglion. To study whether the 5-hydroxytryptamine immunoreactivity in the superior cervical ganglion represented uptake or synthesis of 5-hydroxytryptamine, rats were injected with a specific 5-hydroxytryptamine uptake inhibitor, fluoxetine, 10 mg/kg i.p. twice a day for 5 days, and then they were treated with nialamide and L-tryptophan, as described above. In the superior cervical ganglion of fluoxetine-treated rats, a few 5-hydroxytryptamine-immunoreactive principal nerve and small intensely fluorescent cells, as well as some nerve fibers, were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Simultaneous measurement of oxygen and dopamine: coupling of oxygen consumption and neurotransmission.

Fast-scan cyclic voltammetry was used to simultaneously measure increases in dopamine concentration and decreases in O2 concentration evoked by brief electrical stimulation (two pulses at 10 Hz) in slices of rat caudate nucleus. Dopamine concentration began increasing immediately after the first pulse and reached a maximum within 200 ms of stimulation. The O2 concentration began to decrease 300-700 ms after onset of stimulus. Responses for both dopamine and O2 were dependent on external Ca2+ and were Cd2+ and tetrodotoxin sensitive. Only the O2 response was sensitive to CN- (0.15 mM). At short times after exposure to 50 microM ouabain, electrically stimulated dopamine overflow was increased by 150% and electrically stimulated changes in O2 concentration were unaffected. Maximum dopamine concentration was increased 28% by sulpiride (2 microM), 78% by L-DOPA (60 microM), 105% by nomifensine (10 microM) and unaffected by nialamide (10 microM). Maximum decrease in O2 concentration was increased by 25% by sulpiride and unaffected by nialamide, L-DOPA, or nomifensine. The decreases in O2 concentration are indicative of increased O2 consumption and are a measure of oxidative energy production evoked by electrical stimulation. The increase in dopamine is due to the release of dopamine balanced by uptake and serves as an indication of neurotransmitter activity. The results indicate that increases in oxidative energy production following electrical stimulation are dependent on external Ca2+ entry through Cd(2+)-sensitive channels. Possible mechanisms for this coupling are discussed.

Animals↗

PubMed1982

Genotoxic activity of five antidepressant hydrazines in a battery of in vivo and in vitro short-term tests.

Five antidepressant agents (monoamine oxidase inhibitors) having a hydrazino group--phenelzine, nialamide, mebanazine, isocarboxazid, and iproniazid--were assayed in four in vivo or in vitro short-term tests predictive of the potential carcinogenicity of chemicals. (1) All the compounds tested except iproniazid, produced DNA fragmentation, as evaluated by the alkaline elution technique, in liver and/or lung cells of mice treated ip or po. (2) All the compounds except mebanazine (which was no longer available for testing) were weak inducers of sister chromatid exchanges in bone marrow cells of mice treated ip. (3) Phenelzine and nialamide elicited base-pair substitutions and mebanazine elicited frameshift errors in his- Salmonella typhimurium. S9 mix containing rat liver, mouse liver, or mouse lung S9 fractions had variable effects on mutagenicity. (4) The same three compounds were positive in a DNA repair bacterial test with five trp- Escherichia coli strains lacking a variety of repair mechanisms (uvrA, polA, recA, lexA) or incorporating plasmids (R391).

Animals↗

PubMed1976

Sympathetic nerves to the rat cornea.

The adrenergic innervation of the rat cornea was investigated by using the formaldehyde induced fluorescence (FIF) technique. The fluorescent nerves were observed mainly in the corneal stroma. Either cervical sympathectomy or pre-treatment with reserpine completely abolished the fluorescence of the adrenergic nerves of the cornea. After a stereotactic coagulation of the ophthalmic division of the trigeminal nerve, no adrenergic fibres were visible in the cornea and the number of the fluorescent iridic nerves was also reduced to a marked extent. On the other hand, ciliary ganglionectomy seemed to have no effect on the adrenergic fibres of the cornea. When the rats had been pre-treated with a monoamine oxidase inhibitors, nialamide, and noradrenaline, not only was there an increase in the intensity of the specific fluorescence, but also in the number of adrenergic nerves in the cornea. The epithelium was also shown to contain adrenergic nerves by administering high doses of nialamide combined with noradrenaline, both intravenously as well as topically on the cornea, under the protection of propranolol. It may be concluded that the rat cornea receives its adrenergic innervation along the posterior ciliary nerves. The short ciliary nerves do not appear to carry sympathetic nerves to the cornea.

Animals↗

PubMed1983

Ascorbic acid and membrane ageing: critical determinants of the in-vitro binding of [3H]ADTN to rat striatal tissue.

Tritiated (+/-)-2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene [( 3H]ADTN), binding (0.125-4.0 nM) to rat striatal membranes was investigated using Tris-HCl buffer containing Na2EDTA, nialamide and varying concentrations of ascorbic acid. In the absence of ascorbic acid [3H]ADTN exhibited a high affinity (KD 1.26 nM) saturable binding (Bmax 138 fmol mg-1 protein) (Scatchard analysis). This was not modified by 10(-6) or 10(-5) M ascorbic acid used immediately or 60 min after preparation. However, 10(-4) M ascorbic acid added (within) 15 min after its preparation reduced the number of bindings sites and added 60 min after it also reduced affinity. Ascorbic acid 5.7 mM reduced affinity whether used within 15 min or 60 min of its preparation. When ascorbic acid 10(-4) M was used within 15 min of preparation, and membranes were used immediately, the binding of 2 nM [3H]ADTN was specifically displaceable by nM or sub-nM concentrations of dopamine agonists and antagonists. However, when membranes were used 1-2 h after their preparation there was an increasing loss of the high affinity binding sites displaceable by sub-nM concentrations of (+/-)-ADTN. Thus. [3H]ADTN can be shown to exhibit high affinity stereoselective binding to rat striatal membranes when these are freshly prepared and the assay is performed using Tris-HCl buffer containing nialamide. Na2EDTA and 10(-4) M ascorbic acid prepared within 15 min of use. The characteristics of this binding can be markedly modified if the concentration of ascorbic acid is increased, if its preparation time is extended, or if the membranes are allowed to 'age'.

Animals↗

PubMed1981

Effects from fine muscle and cutaneous afferents on spinal locomotion in cats.

1. The effects of chemically activated fine muscle afferents (groups III and IV) and electrically activated cutaneous afferents on motoneuronal discharges were studied before and during fictive locomotion induced pharmacologically by i.v. administration of nialamide and l-DOPA in high spinal cats. Efferent activity was recorded simultaneously from nerve filaments to ipsi- and contralateral extensor and flexor muscles. In addition, intracellular recordings were made from lumbar alpha-motoneurones.2. After nialamide but before treatment with l-DOPA, in some cases, transient locomotor-like discharges were induced by an increased activity in fine muscle afferents. The response pattern in nerves to both hind limbs could be different showing e.g. only transient alternating activity between knee flexor and extensor of one limb but not of the other one.3. Treatment with l-DOPA did not always cause fictive locomotion. Often not all motoneurone pools showed rhythmic activity. In these cases stimulation of group III and IV muscle afferents usually caused transient periodic activity. In cases with apparent rhythmic activity, algesic stimulation of the gastrocnemius-soleus muscle caused an accentuation of the rhythm by a more abrupt transition from the active phase to the non-active interval. Again, the response patterns on both sides were not uniform in all cases.4. A second type of response to activation of fine muscle afferents had a quite different character: the rhythmic activity was more or less completely overridden by a strong transient tonic hyperactivity or the rhythm was transiently blocked. These phenomena did not occur in the same way in all nerves.5. Electrical stimulation of cutaneous nerves of the hind limb generally induced the same response pattern as chemical stimulation of the group III and IV muscle afferents. The effects varied depending on the stimulus strength and the nerve.6. The results revealed that cutaneous and fine muscle afferents not only have similar functions in the reflex control of a limb but also in evocation and modulation of locomotion. Therefore, it is assumed that both types of afferents may serve together as a peripheral feed-back to the spinal locomotor centre.

Animals↗

PubMed1984

Serotonin-containing neurons in the rat and cat brain, especially in the hypothalamus, following monoamine oxidase inhibitor pretreatment: an immunohistochemical study using anti-serotonin antiserum.

The presence of serotonin-containing neurons in the hypothalamus of the rat and cat was studied by immunohistochemistry. In the rat, a group of serotonin-immunoreactive neurons was observed in the nucleus dorsomedialis hypothalami following nialamide pretreatment at a high dosage (over 300 mg/kg). In the cat, serotonin-immunoreactive neurons were sparsely distributed in the ventral part of the middle to the caudal lateral hypothalamic area after high dosage (500 mg/kg) nialamide pretreatment.

Animals↗

PubMed1977

Uptake of 5-hydroxytryptophan by gustatory cells in the mouse taste bud.

Monoamines in the taste bud cells of the mouse circumvallate papilla were studied by fluorescence histochemistry and electron microscopy. With administration of 5-HTP (5-hydroxytryptophan) after a pretreatment with nialamide, yellow fluorescence appeared in some of the taste bud cells, while no fluorescence was observed in untreated, L-DOPA treated on serotonin treated mice. Electron microscopic study after treatment with both nialamide and 5-HTP showed small dense-cored vesicles intermingled with small clear vesicles (30-60 nm in diameter accumulated at the membranes of the gustatory cells in typical afferent synaptic contacts with nerve terminals. Definite ultrastructural change in large dense-cored vesicles (70-100 nm in diameter) could not be observed. It is suggested that the gustatory cells of the mouse take up 5-HTP and convert it to serotonin. The synaptic vesicles in the gustatory cells are believed capable of storing and releasing serotonin which presumably acts as the neurotransmitter involved in the impulse transmission from the gustatory cells to the sensory nerve fibers.

5-Hydroxytryptophan↗

PubMed1975

[Fluorohistochmical studies on localization of 5-hydroxytryptamine neurons in the rat brain following administration of thiopental sodium].

The localization of 5-hydroxytryptamine (5-HT) neurons in the rat brain was studied by the fluorescence histochemical method of Falck and Hillarp. A model experiment and tissue experiment were used to measure the characteristics of wave length of 5-HT fluorophor and we decided 420 mmu for excitation maxima and 520 mmu for emission maxima. The 5-HT neurons both in frontal and sagittal sections of the brain from reserpine-nialamide-treated rats were observed fluorohistochemically. The brain was divided into 5 portions; medulla oblonga, pons, midbrain, diencephalon and telencephalon. In frontal sections, from B1 to B8 cell groups were localized in raphe nuclei, in the region of 200 mu width on both sides from the central plane, excluding most of B2 cells and cells of B9 group which were situated on both side apart from the central plane. Microphotographs taken from about 34 areas of a sagittal section were composed to determine the interrelationship between B cell groups of 5-HT neurons. The frontal sections untreated with reserpine-nialamide showed a faint fluorescence of 5-HT neurons, however, after the administration of thiopental sodium 80 mg/kg i.p. the fluorescence of 5-HT neurons was increased in intensity and the observable cells were increased in number, especially in the B7 cell group. The yellow fluorescence of 5-HT nerve terminals in nuc suprachiasmaticus in the sagittal section was increased in intensity and varicosities of the terminals were readily observed. These results verified the increase of 5-HT in 5-HT neurons after the administration of thiopental and suggest that the 5-HT neuron may play a role in the mechanism of the central action of a thiopental.

Animals↗

PubMed1992

[Toxic polyneuropathies].

Toxic factors may have damaging effects on the peripheral nerves at different sites: on the axon, on the myelin sheath, on the cell bodies and on the vasa nervorum. The toxic neuropathies can be divided up into polyneuropathies induced by drugs, by industrial, environmental and stimulant poisons. Mostly symmetrical sensory symptoms and signs are the first disturbances, often followed by symmetrical motor pareses. Some polyneuropathies induced by amiodarone, benzene, lead, cimetidine, chloroquine, dapsone, gentamycin, gold, imipramine, hexacarbons, nialamide, penicillin, triorthocresylphosphate and vincristine are primarily dominated by motory losses. Polyneuropathies induced by amitriptyline, ethylene, oxide, lead, chlorprothixene, heroin, hydralazine, methaqualone, nialamide and penicillin show an asymmetrical distribution pattern of the neural losses. In some types of toxic polyneuropathies the cranial nerves and the autonomic nerves are particularly involved. The clinical symptomatology of the most important types of toxic neuropathies are described shortly. The best therapy is, of course, termination of exposure to the toxic substance concerned.

Diagnosis, Differential↗

PubMed1965

[Effect of the activity of an indirect anticoagulant by a monoamine oxidase inhibitor].

The combinations of some anticoagulants (phenindione, chlorphenadione, diphenadione, phenprocoumon, 3-[1-(p-chlorophenyl)propyl]-4-hydroxycoumarin, cumachlor and acenocoumarol) with MAO-inhibitors (phenylcyclopropylamino hydrochloride, isocarboxazid, iproniazid, nialamide and p-chloro-N'-[2-(isopropylcarbamoyl)-1-methylethyl]benzohydrazide) were investigated with regard to modification of the anticoagulant activity in the rat. The activity of some anticoagulants like phenindione may be enhanced by the addition of MAO-inhibitors, whereas others (chlorphenadione, phenprocoumon) are only slightly or not at all influenced. The MAO-inhibitors phenylcyclopropylamino hydrochloride and nialamide show enhancement of activity in most combinations whereas iproniazid never does. The other MAO-inhibitors lie between these two extremes.

Animals↗

PubMed1988

Effects of imipramine-like drugs and serotonin uptake blockers on delay of reward in rats. Possible implication in the behavioral mechanism of action of antidepressants.

This study investigated in rats the action of a variety of antidepressants in two behavioral models. In model 1, animals trained in a T-maze were allowed to choose between 2 magnitudes of reward: immediate but small reward (2 pellets) vs. a 25-sec delayed but large reward (10 pellets). Under this alternative, vehicle-injected rats selected the large-but-delayed reward in less than 40% of the trials. Desipramine 8 mg/kg, clomipramine 8 mg/kg, maprotiline 8 mg/kg, indalpine 2 to 4 mg/kg, zimelidine 8 to 16 mg/kg, nialamide 16 to 32 mg/kg and clenbuterol 0.03 to 0.06 mg/kg significantly increased the number of choices of the large-but-delayed reward. In model 2, rats were subjected to a fixed ratio 48 schedule of food reinforcement; after completion of a series of exactly 48 presses a food pellet was delivered, and if no further press occurred, a sequence of free pellets was initiated according to fixed, increasing intervals (from 5-80 sec). Pressing during the sequence stopped it and required the rat to complete again the fixed ratio 48 to be reinforced and to reintiate the sequence. Waiting for free reward was significantly lengthened by desipramine 8, clomipramine 16, indalpine 8, zimelidine 8 to 16, nialamide 32 and clenbuterol 0.007 to 0.06 mg/kg. These results suggest that, possibly through noradrenergic and serotonergic mechanisms, antidepressants markedly enhanced rats' ability to wait for food reward, an affect which might reflect the ability of these drugs to improve impulse control. The relevance of such a property in the therapeutic action of antidepressants remains to be delineated.

Animals↗