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PubMed2005

Possible association between autism and variants in the brain-expressed tryptophan hydroxylase gene (TPH2).

We report a possible association between autism in our sample and a recently described brain-expressed tryptophan hydroxylase gene (TPH2). The well-replicated involvement of the serotonin neurotransmitter system in autism has stimulated interest in many genes in the serotonin pathway as possible candidates for mutations leading to autism susceptibility. Serotonin synthesis is controlled by the rate-limiting enzyme tryptophan hydroxylase. A mouse study of the original tryptophan hydroxylase gene (TPH1) and the new isoform (TPH2) showed that while TPH1 is primarily expressed peripherally, TPH2 is found exclusively in brain tissue. We searched for human sequence variants in 6,467 nucleotides covering all 11 exons of TPH2, and also 248 nucleotides upstream of the start codon, and 935 nucleotides downstream of the stop codon. Eighteen variants were characterized in 88 subjects with autism studied at our two centers, and 95 unrelated control subjects. Using a model-free association method and empirical P value estimation, two variants showed frequency differences between autism and control subjects (P = 0.01 for a T-G variant in intron 1, and P = 0.02 for a A-T variant in intron 4). A haplotype including these variants showed slightly increased significance (P = 0.005). Further investigation of clinical phenotypes showed a possible association between presence of the variants at these two SNPs and higher scores on the Autism Diagnostic Interview (ADI) domain describing repetitive and stereotyped behaviors (P = 0.007). We conclude that TPH2 may play a modest role in autism susceptibility, perhaps relating specifically to repetitive behaviors, pending replication of this result.

Autistic Disorder↗
PubMed2002

Factors predicting increased incidence of abnormal behavior in male pigtailed macaques.

To identify factors predicting abnormal behavior in laboratory monkeys, we observed all available singly housed 4- to 11-year-old male pigtailed macaques (Macaca nemestrina), the species/age/sex group most likely to be referred to the Washington National Primate Research Center's Psychological Well-Being Program for behavioral assessment. Of the 87 subjects, 29 had been referred to the program whereas 58 had not. Abnormal behavior was unrelated to the subject's housing location (biocontainment vs. other facility) or invasiveness of research. Nursery-reared subjects displayed more abnormal behavior than mother-reared subjects. Across and within rearing categories, the proportion of the first 48 months of life spent singly housed was positively related to the amount of abnormal behavior at maturity. This effect was stronger for subjects separated from the mother for clinical rather than experimental reasons, and least for mother-reared subjects. Locomotor stereotypy, by far the most frequent form of abnormal behavior, was positively related to time in single housing but was unrelated to rearing. These results reinforce the importance of tactile social contact during juvenility for the prevention of abnormal behavior in social primates. They also suggest that self-directed abnormal behaviors and locomotor stereotypies have different etiologies.

Aging↗
PubMed1982

Hysterical seizures: suggestion as a provocative EEG test.

We studied 57 patients with poorly controlled or atypical seizures to identify hysterical attacks with a provocative test consisting of initiation and termination of an attack with suggestion and saline injection during electroencephalographic (EEG) monitoring. Using this method, we diagnosed 48 patients as having hysterical attacks. Three additional patients had spontaneous hysterical attacks during routine recordings. Of the 51 patients with hysterical attacks, 78% were female. Two-thirds of the patients were between the ages of 20 and 35 years. Thirty-two patients had taken anticonvulsants before the study. Each patient's hysterical attack, aura, and postictum was stereotyped, and the 6 patients subject to both hysterical and organic seizures described the two types of attacks as different stereotyped behaviors. Tongue laceration, urinary incontinence, and postictal confusion were common. Twelve patients had evidence of past or present neurological disease. Abnormal EEGs were recorded in 37% but only 12% had spike or spike and wave discharges. The provocative EEG test employing saline and suggestion is a useful tool in the diagnosis of hysterical "seizures."

Adolescent↗
PubMed1991

Effects of exposure to a 60-kV/m, 60-Hz electric field on the social behavior of baboons.

We found in a previously reported study that exposure to a 30-kV/m, 60-Hz electric field had significant effects on the social behavior of baboons. However, it was not established whether or not the effects were related specifically to the 30-kV/m intensity of the field. A new experiment was conducted to determine whether or not exposure to a 60-Hz electric field at 60 kV/m would produce like changes in the baboons' social behavior. We exposed one group of eight male baboons to an electric field 12 hours a day, 7 days a week, for 6 weeks. A second group of eight animals was maintained under sham-exposure (control) conditions. Rates of performing on each of six categories of social behavior and on four categories of nonsocial behavior were used as criteria for comparing exposed with unexposed subjects and for within-group comparisons during three six-week experimental periods: Pre-Exposure, Exposure, and Post-Exposure. The results indicate that (1) during the exposure period, exposed animals exhibited statistically significant differences from controls in means of performance rates based on several behavioral categories; (2) across all three periods, within-group comparisons revealed that behaviors of exposed baboons were significantly affected by exposure to the electric field; (3) changes in performance levels probably reflect a stress response to the electric field; and (4) the means of response rates of animals exposed at 60 kV/m were higher, but not double, those of animals exposed at 30 kV/m. As in the 30-kV/m experiment, animals exposed at 60 kV/m exhibited significant differences in performances of Passive Affinity, Tension, and Stereotypy. Mean rates of performing these categories were 122% (Passive Affinity), 48% (Tension), and 40% (Stereotypy) higher in the exposed group than in the control group during exposure to the 60-kV/m field.

Animals↗
PubMed1995

Effects of concurrent exposure to 60 Hz electric and magnetic fields on the social behavior of baboons.

Our previous research has demonstrated that 30 or 60 kV/m electric fields (EF) reliably produce temporary increases in the performance of three categories of baboon social behavior: Passive Affinity, Tension, and Stereotypy. The experimental design included 6 week preexposure, exposure, and postexposure periods with experimental and control groups, each with eight subjects. Here, we report two experiments that evaluated the effects of combined EF and magnetic fields (MF) on baboon social behavior. One experiment demonstrated that exposure to 6 kV/m EF and 50 microT (0.5 G) MF produced Period x Group interactions for Stereotypy and Attack, but the previously observed increases in Passive Affinity, Tension, and Stereotypy did not occur. A second experiment demonstrated that exposure to 30 kV/m EF and 100 microT 1.0 G MF did not produce the same magnitude of increases in Passive Affinity, Tension, and Stereotypy observed previously with 30 kV/m EF alone. The exposed group exhibited decreased performance rates for several behavior categories during exposure with further declines during postexposure. The control group showed fewer downward trends across periods.

Animals↗
PubMed2003

Distribution of dendrites of descending neurons and its implications for the basic organization of the cockroach brain.

To determine precisely the brain areas from which descending neurons (DNs) originate, we examined the distribution of somata and dendrites of DNs in the cockroach brain by retrogradely filling their axons from the cervical connective. At least 235 pairs of somata of DNs were stained, and most of these were grouped into 22 clusters. Their dendrites were distributed in most brain areas, including lateral and medial protocerebra, which are major termination areas of output neurons of the mushroom body, but not in the optic and antennal lobes, the mushroom body, the central complex, or the posteroventral part of the lateral horn. The last area is the termination area of major types of olfactory projection neurons from the antennal lobe, i.e., uni- and macroglomerular projection neurons, so these neurons have no direct connections with DNs. The distribution of axon terminals of ascending neurons overlaps with that of DN dendrites. We propose, based on these findings, that there are numerous parallel processing streams from cephalic sensory areas to thoracic locomotory centers, many of which are via premotor brain areas from which DNs originate. In addition, outputs from the mushroom body, central complex, and posteroventral part of the lateral horn converge on some of the premotor areas, presumably to modulate the activity of some sensorimotor pathways. We propose, based on our results and documented findings, that many parallel processing streams function in various forms of reflexive and relatively stereotyped behaviors, whereas indirect pathways govern some forms of experience-dependent modification of behavior.

Animals↗
PubMed1977

Effects of maternal mobility, partner, and endocrine state on social responsiveness of adolescent rhesus monkeys.

The social behavior of rhesus monkeys raised for the 1st year of life with mobile (MS) or stationary (SS) cloth surrogate mothers was investigated when the animals reached 4-5 yr of age. The MS males generally refrained from social interaction during initial pairings with females, whereas SS males interacted frequently, but were more often the targets of attacks and chases from adult females than were MS males. The MS males were more likely to vary their social behavior according to the behavior of the social partner and seemed to benefit more from extended social exposure than their SS counterparts. The MS females were more similar to wild-born females than were SS females in nearly every behavior category and dimension tested. These results suggest that rearing with mobile artificial mothers improves the chances of later adaptive social adjustments in socially restricted monkeys.

Age Factors↗
PubMed2003

A systems neuroscience approach to autism: biological, cognitive, and clinical perspectives.

Autism is a behaviorally defined disorder characterized by a broad constellation of symptoms. Numerous studies directed to the biological substrate demonstrate clear effects of neurodevelopmental differences that will likely point to the etiology, course, and long-term outcomes of the disorder. Consistently replicated research on the neural underpinnings of autism is reviewed. In general, results suggest several main conclusions: First, autism is a heterogeneous disorder and is likely to have multiple possible etiologies; second, structural brain studies have indicated a variety of diffuse anatomical differences, reflective of an early developmental change in the growth or pruning of neural tissue, rather than localized lesions; similarly, neurochemical studies suggest early, neuromodulatory discrepancies rather than gross or localized abnormalities; and finally, there are a number of limitations on studies of brain activity that to date preclude definitive answers to questions of how the brain functions differently in autism. The large number of active research programs investigating the cognitive neuroscience of autism spectrum disorders, in combination with the exciting development of new methodologies and tools in this area, indicates the drama and excitement of work in this area.

Autistic Disorder↗
PubMed2006

Effects of repeated phencyclidine administration on adult hippocampal neurogenesis in the rat.

Dysfunctional maturation of neural networks, particularly hippocampus-prefrontal networks, may be of particular interest in determining the pathophysiology of schizophrenia. Phencyclidine (PCP)-induced symptoms in humans appear to offer a more complete model of schizophrenia than do amphetamine-induced symptoms. This study investigated the effects of intermittent i.p. injections of PCP (7.5 mg/kg) on cell proliferation and survival of granule cells in the dentate gyrus of the rat brain using quantitative immunohistochemical techniques for 5-bromo-2'-deoxyuridine (BrdU)-positive cells. After repeated PCP injection for 14 days, mean scores for stereotyped behavior increased with the number of injections, while scores for ataxia and backpedaling as serotonergic behaviors gradually decreased. The number of BrdU-positive cells decreased by 23% in the subgranular zone of the dentate gyrus by 24 h after repeated injections. However, decreased levels of BrdU-positive cells returned to control levels within 1 week. Differentiation of newly formed cells was not influenced. Repeated PCP administration after BrdU injection did not exert any effects on survival of newly generated cells. These findings suggest that transient disturbances of cell proliferation in the dentate gyrus occur under PCP-related behavioral abnormalities. Whether disturbed cell proliferation would thus be closely implicated in the development of behavioral sensitization induced by PCP administration is unclear, but this would possibly result from adaptation to new pharmacological conditions under behavioral sensitization or stressful conditions of PCP-related abnormal behaviors. Further studies are required to elucidate the biological significance of hippocampal neurogenesis in the mechanisms underlying the development of cognitive dysfunctions and the psychosis of schizophrenia.

Animals↗
PubMed2000

Psychological state and mood effects of steroidal chemosignals in women and men.

We tested the hypothesis that isolated steroids, claimed to act like pheromones, affect human psychological state or mood. In the first experiment, we established that two steroids, Delta4, 16-androstadien-3-one and 1,3,5(10)16-estratetraen-3-ol, modulated emotional states within 6 min of exposure. In men and women, neither steroid had specific effects on states of alertness or negative-confused mood. However, both steroids increased positive stimulated mood state in women but decreased it in men. These psychological findings do not parallel the reported sexually specific effects of these two steroids on the surface potential activity of putative vomeronasal epithelium. In a second experiment on women, we replicated that Delta4,16-androstadien-3-one modulated their general mood state, even when women were not aware of its odor and gave identical olfactory descriptions for the steroid and the control carrier solutions. In this within-subjects, repeated-measures experiment, androstadienone prevented the deterioration in general mood which occurred during exposure to the clove oil carrier solution in the laboratory environment. Thus, androstadienone appears to modulate affect, rather than releasing stereotyped behaviors or emotions. It is premature to call these steroids human pheromones. They are nonetheless psychologically potent, mandating future work delineating their function-i.e., whether these steroids are communicative chemosignals, context specific, or related to unconscious associations. In light of these modulatory effects and the complexity of human behavior, the function of chemosignals and pheromonal systems in a variety of species may need to be expanded to include the concept of modulators, as well as the traditional releasers, primers, and signaling compounds.

Adult↗
PubMed1996

Triadimefon and triadimenol: effects on monoamine uptake and release.

Acute administration of the agricultural fungicide triadimefon produced a neurotoxic syndrome in rats characterized by increased motor activity, stereotyped behaviors, and altered monoamine metabolism. Triadimenol, a metabolite of triadimefon in mammals, plants, and soil, also increased motor activity in rodents. To test the hypothesis that triadimefon and triadimenol are indirect-acting dopamine agonists, the present studies examined their abilities to inhibit monoamine uptake, bind to the dopamine transporter, and stimulate dopamine efflux in rat brain tissue, in vitro. Both triazoles inhibited the uptake of dopamine in striatal synaptosomal preparations. Triadimefon was 100-fold less potent than GBR12909, a prototypical inhibitor of dopamine uptake (IC50 = 4.7 microM vs. 37.2 nM, respectively), and triadimenol was about three-fold less potent than triadimefon. Triadimefon also weakly inhibited the uptake of norepinephrine in cortical synaptosomes (IC50 = 22.4 microM), but neither compound blocked the uptake of serotonin in cortical synaptosomes (IC50s > 100 microM). Triadimefon and triadimenol had similar affinity for [3H]mazindol binding sites on the dopamine transporter (IC50s approximately 1-1.5 microM, only two- to threefold greater than GBR12909). Neither triadimefon nor triadimenol (0.01-100 microM) increased basal efflux of [3H]DA that had been preloaded into striatal minces in vitro. An unexpected result was that GBR12909 (10 microM) increased basal efflux of [3H]DA by 71%, suggesting that this compound has DA releasing properties. These data suggest that increased synaptic concentrations of dopamine due to inhibition of dopamine uptake may play an important role in the neurobehavioral effects of triadimefon and triadimenol.

Animals↗
PubMed2003

Prevention of epileptic seizures by taurine.

Parenteral injection of kainic acid (KA), a glutamate receptor agonist, causes severe and stereotyped behavioral convulsions in mice and is used as a rodent model for human temporal lobe epilepsy. The goal of this study is to examine the potential anti-convulsive effects of the neuro-active amino acid taurine, in the mouse model of KA-induced limbic seizures. We found that taurine (43 mg/Kg, s.c.) had a significant antiepileptic effect when injected 10 min prior to KA. Acute injection of taurine increased the onset latency and reduced the occurrence of tonic seizures. Taurine also reduced the duration of tonic-clonic convulsions and mortality rate following KA-induced seizures. Furthermore, taurine significantly reduced neuronal cell death in the CA3 region of the hippocampus, the most susceptible region to KA in the limbic system. On the other hand, supplementation of taurine in drinking water (0.05%) for 4 continuous weeks failed to decrease the number or latency of partial or tonic-clonic seizures. To the contrary, we found that taurine-fed mice showed increased susceptibility to KA-induced seizures, as demonstrated by a decreased latency for clonic seizures, an increased incidence and duration of tonic-clonic seizures, increased neuronal death in the CA3 region of the hippocampus and a higher post-seizure mortality of the animals. We suggest that the reduced susceptibility to KA-induced seizures in taurine-injected mice is due to an increase in GABA receptor function in the brain which increases the inhibitory drive within the limbic system. This is supported by our in vitro data obtained in primary neuronal cultures showing that taurine acts as a low affinity agonist for GABA(A) receptors, protects neurons against kainate excitotoxic insults and modulates calcium homeostasis. Therefore, taurine is potentially capable of treating seizure-associated brain damage.

Animals↗
PubMed1985

Clinical activity of GABA agonists in neuroleptic- and L-dopa-induced dyskinesia.

It is well known that the therapeutic effect of neuroleptics is counterbalanced by the property of these drugs to induce serious neurological side-effects mainly represented by tardive dyskinesia. Several reports indicate that at the experimental level GABA agonists interact with dopamine neurons with effects on behavior, stereotyped and dyskinetic movements induced by either lesions or dopamine agonists. This action on dopamine-related events provides a basis for a possible therapeutic action of GABA agonists in dyskinesia. Previous results with the GABA agonists muscimol and THIP in tardive dyskinesia have not been encouraging. The present paper deals with clinical results obtained with the new GABA agonist progabide both in neuroleptic-induced dyskinesia and in L-dopa-induced dyskinesia from five studies conducted on a total of 57 patients. Twenty-nine patients suffering from neuroleptic-induced dyskinesia have been treated in three studies (two open, one double-blind cross over) with progabide at doses from 900 to 2400 mg/day; clinical evaluation and EMG testing are in favor of a therapeutic effect of progabide on dyskinesia. Twenty-eight patients with L-dopa dyskinesia have been studied in two double blind trials. At variance with studies in tardive dyskinesia progabide was not effective in this kind of dyskinesia but an increase in the "on" time has been observed in both studies. Attempts to treat tardive dyskinesia with various pharmacological tools are reviewed and discussed, showing that at present no established effective treatment exists for this frequent complication of neuroleptic use. The possible mechanism of action of progabide in dyskinesia is discussed in the light of its pharmacological properties. These results suggest that progabide can be useful in the treatment of neuroleptic-induced dyskinesia.

Antipsychotic Agents↗
PubMed1989

Cholinomimetic activities of minaprine.

The cholinomimetic activities of the antidepressant drug minaprine have been investigated, in vitro and in vivo, in rodents. Minaprine, and its metabolite SR 95070B [3-(2-morpholinoethylamino)-4-methyl-6-(2-hydroxyphenyl) pyridazine hydrochloride] selectively displaced [3H]-pirenzepine from its cortical and hippocampal binding sites, and only weakly inhibited the binding of [3H]-N-methylscopolamine in either the rat cerebellum, heart and salivary glands, or the guinea-pig ileum. In mice, none of these drugs induced the typical cholinergic side-effects up to lethal doses. Minaprine and SR 95070B antagonized rotations induced by an intrastriatal injection of pirenzepine in mice, after intraperitoneal and/or oral administration. Minaprine also antagonized atropine-induced mydriasis in mice. Both minaprine and SR 95070B potentiated the tremorigenic effect of oxotremorine without inducing tremor when injected alone. Finally, minaprine and SR 95070B, after parenteral and/or oral injection, antagonized the scopolamine-induced deficit in passive avoidance learning, and enhanced short-term retention in the social memory test, in rats. The muscarinic agonists arecoline, oxotremorine and RS 86 [2-ethyl-8-methyl-2,8 diazaspiro-4,5 decan-1,3 dion hydrobromide], as well as the acetylcholine esterase inhibitors physostigmine and tacrine were active in most of these models. These results indicate that minaprine, and its metabolite SR 95070B, have cholinomimetic activities which could be, at least in part, mediated by their selective affinity for M1 muscarinic receptors. Thus minaprine could represent a potential useful drug for the treatment of senile dementias and cognitive impairments occurring in elderly people.

Animals↗
PubMed1982

Histidyl-proline diketopiperazine: its biological role as a regulatory peptide.

Histidyl-proline diketopiperazine [cyclo(His-Pro)] is a metabolite of thyrotropin releasing hormone (TRH). This review summarizes the literature concerning cyclo (His-Pro) and, in addition, some studies dealing with TRH and other peptide that are considered of interest. The enzymes concerned with the metabolism of TRH are discussed. Distribution studies of peptides by immunological methods show that, while TRH is concentrated in synaptosomes, cyclo (His-Pro) is not, suggesting that cyclo (His-Pro) is not a classical neurotransmitter. Rat brain contains approximately three times as much cyclo (His-Pro) as TRH, mainly localized in the pituitary and hypothalamus. While the TRH is found in a free form, the cyclo (His-Pro) is bound to a carrier of molecular weight approximately 70,000. While specific membrane receptors for TRH have been detected in pituitary cells, no such receptors for cyclo (His-Pro) have yet been found in brain or pituitary; however, there is a specific binding of cyclo (His-Pro) to adrenal cortex membranes. Both TRH and cyclo (His-Pro) have effects in the central nervous system or pituitary. These include effects on prolactin release, thermoregulation, CNS depression, stereotypic behavior and cyclic nucleotide levels. Possible mechanisms and interrelations of these effects are discussed.

Animals↗
PubMed1995

Dementia lacking distinctive histopathology: clinicopathological evaluation of 32 cases.

We report the neuropathological findings in 32 patients, aged 46-86 years, with dementia lacking distinctive histopathology. All of the patients were classified clinically as having Pick's or atypical Pick's disease, but the routine neuropathological evaluation showed no specific histopathological changes such as Pick bodies, senile plaques, neurofibrillary tangles or Lewy bodies. In 50% of the cases the first symptoms appeared before 65 years of age. However, there were 9 patients with onset in the eighth decade. Positive family history was found only in 6 presenile cases. The retrospective evaluation of the clinical records revealed the consistent presence of "frontal" symptomatology, including loss of personal awareness, inappropriate euphoria and stereotyped behavior. Speech disorders were observed in 80% of the cases, whereas temporospatial disorientation and memory impairment were less frequent. Praxis and gnosis were strikingly preserved in most of the cases. The macroscopic neuropathological examination revealed frontal or temporopolar atrophy in 97% of the cases, while the hippocampus and subcortical structures were relatively spared in the majority of the cases. Histologically, four groups were recognized. Group A showed moderate to severe neuron loss and gliosis in the frontal and/or temporopolar cortex without subcortical involvement. In group B, the neocortical cell loss was widespread, and the striatum and substantia nigra displayed differential degrees of gliosis but no neuron loss. Group C patients showed a lesion distribution comparable to that observed in group B but with severe neuron loss in at least one subcortical region. Four cases formed group D, which was characterized by the preservation of the pyramidal neurons in the neocortex and variable subcortical changes. Despite these differences in the topography of pathological changes, all of the cases shared a similar clinical profile. These findings further demonstrate the epidemiological and neuropathological heterogeneity of dementia lacking distinctive histopathology. Furthermore, they suggest that the same clinical manifestations may correspond to several distinct pathological processes in this condition.

Age Distribution↗
PubMed1975

Monkey motor stimulation and altered social behavior during chronic methadone administration.

To assess the effects of chronic methadone administration on locomotor, social, and eating behavior od drug-native individuals under circumstances approximating those of methadone "maintenance" clinics, we gave single, daily oral doses of methadone to 5 Macaca radiata monkeys living in a social group. We obtained motor activity counts automatically during 6 weeks of baseline, 10 weeks of drug administration, and 3 weeks of post-drug abstinence. Social behaviors of association, dominance, submission, and sexuality were counted 5 days per week, and animal weights, food eaten and food-reinforced work were recorded. Plasma methadone levels were near those achieved in mechadone clincs. Methadone produced mixed stimulation and sedation in the daytime, with stimulation predominating for 4 hrs following administration. At night the subjects moved less while taking the drug. Associative behaviors were reduced by methadone, but dominance, submission, and sexual behaviors were not altered. The monkeys ate less while taking the drug, losing weight and working less for food. In these primates methadone had significant stimulant properties, impaired important social behaviors, and reduced the potency of food as a reinforcer of work. The results are compared with methadone's effects upon humans.

Animals↗
PubMed1976

Comparison of the effects of morphine, pentazocine, cyclazocine and amphetamine on intracranial self-stimulation in the rat.

Rats were trained to press a lever in order to stimulate their hypothalamus through a chronically implanted electrode. Dose-response curves were determined for the effects of morphine (0.3-10 mg/kg), pentazocine (1.0-30 mg/kg), cyclazocine (0.03-30 mg/kg) and d-amphetamine (0.1-3.0 mg/kg) on responding for intracranial stimulation, and then were redetermined in the presence of one or two doses of naloxone. The three analgesics produced only dose-related decreases in responding with the following relative potencies: cyclazocine greater than morphine greater than pentazocine. The well-documented rate-increasing effects of d-amphetamine on intracranial self-stimulation were observed at 0.3 and 1.0 mg/kg of the drug; decreases in responding at 3.0 mg/kg were associated with stereotyped behavior. Naloxone, which had no effect of its own on self-stimulation, increased the dose of the analgesics required to depress response rate in a manner consistent with a competitive antagonism. In contrast, response rates at all doses of d-amphetamine tested in the presence of naloxone. Thus, the interaction between naloxone and d-amphetamine is qualitatively different from the one between naloxone and the analgesics. This finding extends to intracranial self-stimulation the generality of a previous report of interactions between d-amphetamine and naloxone on behavior in the rat.

Animals↗