Central noradrenaline depletion attenuates amphetamine-induced locomotor behavior (original) (raw)
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The Effect of Amphetamine on Locomotion Depends on the Motor Device Utilized
Pharmacology Biochemistry and Behavior, 2000
DELLA MAGGIORE, V. AND M. R. RALPH. The effect of amphetamine on locomotion depends on the motor device utilized: The open field vs. the running wheel. PHARMACOL BIOCHEM BEHAV 65 (4) 585-590, 2000.-The effect of amphetamine on the level of locomotion exhibited on two different motor devices was examined in the Golden hamster.
Psychopharmacology, 2009
Rationale Most drugs of abuse stimulate both locomotor activity and the hypothalamic-pituitary-adrenal (HPA) axis, but the relationship between the two responses within the same subjects and their reliabilities has been scarcely studied. Our objectives were to study: (1) the consistency and stability across time of locomotor and HPA activation induced by repeated d-amphetamine (AMPH); (2) the relationship between locomotor and hormonal responses to AMPH; and (3) the relationship between noveltyinduced activity and both types of responses to the drug. Methods Male adult rats were exposed to a novel environment to study the locomotor response. Later, they were injected with AMPH (2 mg/kg, sc) for 5 days. In Experiment 1, Plasma adrenocorticotropin (ACTH) and corticosterone levels in response to AMPH were studied on days 1, 3, and 5, and locomotor response on days 2 and 4. In Experiment 2, ACTH and corticosterone responses were studied on days 2 and 4, and locomotor response on days 1, 3, and 5.
Psychopharmacology, 1999
Rationale and objectives: In order to assess directly the relationship between locomotor activity and drug self-administration, the present experiment simultaneously measured these two behaviors in rats with different histories of pre-exposure to amphetamine either following or in the absence of priming injections of the drug. Methods: Different groups of rats were exposed to ten daily injections of either saline (1.0 ml/kg, i.p.) or amphetamine (1.5 mg/kg, i.p.) and, in each of 13 daily sessions starting 10 days later, were given the opportunity to lever press for a low dose of amphetamine (10 µg/kg per i.v. infusion) in a two-lever (active versus inactive) continuous reinforcement task. Animals were administered a priming injection of amphetamine (1.0 mg/kg, i.p.) immediately before testing on the first 8 days, a saline injection (1.0 ml/kg, i.p.) on the next 3 days and amphetamine on the final 2 days of testing. Results: Consistent with previous reports, prior exposure to amphetamine led to an enhanced locomotor response to the priming injection of amphetamine on the first day of testing. Little pressing for drug was observed on this day. Following priming injections on the subsequent test days, evidence for enhanced locomotion by amphetamine-pre-exposed rats diminished and both groups showed comparable and progressive increases in active versus inactive lever pressing. When priming injections were not made, however, only animals previously exposed to amphetamine maintained lever pressing for the drug. Under these conditions, these animals emitted more active lever presses and time-out responses and exhibited higher levels of locomotor activation in proximity to the active drug administering lever than did salinepre-exposed rats. Conclusions: These results are consistent with the view that previous exposure to amphetamine produces a long-lasting enhancement in the behavioral activation animals will direct toward stimuli as-sociated with the drug. This enhancement was displayed initially as a sensitized locomotor response to amphetamine on the first day of testing and was subsequently observed on those test days when no priming injections were given when animals continued to self-administer a low dose of amphetamine under a simple schedule of reinforcement. The implications of these findings for our understanding of the excessive expression of drug-directed behaviors are discussed.
Neuroscience Letters, 1983
Male rats received the noradrenaline neurotoxin DSP4 (50 mg/kg) 7 days prior to injection of Damphetamine (10 or 40/zmol/kg i.p.). The hyperactivity induced by D-amphetamine (10 pmol/kg) was significantly reduced by DSP4 pretreatment. However, the increased rearings and the amphctamine-indlJced stereotypies were not blocked by pretreatment with DSP4. The reduction of amphetamine hyperactivity induced by DSP4 was blocked by pretreatment with the nora0renaline-uptake blocking agent, desipramine, which prevents the neurotoxic action of DSP4. The presem results suggest a selective involvement of central noradrenergic neurones in the locomotor stimulant effect of amphetamine in the rat.
A novel procedure for dissociating the anatomical bases of the behavioral effects of amphetamine
Pharmacology Biochemistry and Behavior, 1987
TOWELL, A , P WILLNER AND R MUSCAT A novel procedure for dtssoctatmg the anatomtcal bases of the behaworal effects of arnphetamtne PHARMACOL BIOCHEM BEHAV 28(3)423-426, 1987 --A novel operative procedure is described in which the same cannula may be used to administer drugs e~ther to the caudate nucleus (CN) or to the nucleus accumbens (NAcc) of the rat M~croinject~ons of amphetamine (10 or 20/xg) into the CN produced a reliable and robust stereotyped response, when admlmstered to the NAcc of the same ammai the higher dose increased locomotor activity The stereotypy following peripheral administration of amphetamine (5 mg/kg) was antagonlsed by Infusions of halopendol (30/~g) into the CN but not into the NAcc Conversely, the locomotor activity following a lower dose of amphetamine (1 mg/kg) was antagomsed by tnfuslons of halopendol (5 gg) ~nto the NAcc but not into the CN The results confirm earlier reports that d~fferent anatomical structures mediate the behavioral effects of low and high doses of amphetamine Amphetamine Haloperldol Locomotor act~wty Stereotyped behavior Dopamme Caudate nucleus Nucleus accumbens Rat
Psychopharmacologia, 1975
Locomotor activity and Y-maze spontaneous alternation were examined in three strains of inbred mice (A/J, DBA/2J and C57BL/6J) following various drug treatments. Although the strains exhibited different levels of locomotor activity, the level of spontaneous alternation was comparable among the strains. Scopolamine produced dose dependent increases in locomotor activity in the A and DBA/2 strains, but produced a transient inhibitory effect upon locomotor activity in C57BL/6. Nevertheless, spontaneous alternation was eliminated equally, regardless of strain, d-Amphetamine increased locomotor activity and reduced alternation significantly below chance levels (perseveration). s-Methyl-ptyrosine (e-MpT) and FLA-63 reduced the locomotor stimulating effects of d-amphetamine; however, the effectiveness of these agents was found to be strain dependent. Neither ~-MpT nor FLA-63 reduced the perseverative behavior. A subsequent study employing Swiss-Webster mice revealed that with pretreatment of reserpine, both e-MpT and FLA-63 eliminated the amphetamine-induced perseverative behavior. Results were interpreted in terms of (a) the role of cholinergic and catecholaminergic systems in modulating alternation behavior, (b) qualitative differences in the behavioral effects elicited by scopolamine and d-amphetamine, (c) strainspecificity regarding pharmacological effects, and (d) role of newly synthesized norepinephrine and dopamine in subserving amphetamine-induced locomotor activity and perseveration.
Pharmacology Biochemistry and Behavior, 2011
The goal of the study was to measure spontaneous and amphetamine-induced motor and locomotor activity in three selectively bred lines of male Long-Evans rats. The number of 50 kHz ultrasonic vocalizations (USVs) emitted in response to heterospecific play with human hand ("tickling") had been measured daily in these lines of rats from 21 to 24 days of age, as a criterion for dividing them into high vocalizing line, low vocalizing line, and random breeding and testing lines. This study sought to determine whether selection of rats based on their affective social-vocalizations also had effects on their locomotor performance and sensitivity to amphetamine. In this study adult animals from the 25th generation (with no further selection) were tested. The results showed that rats, which were selectively bred to emit high numbers of 50 kHz vocalizations, also exhibited elevated levels of spontaneous locomotor activity. After systemic injection of D-amphetamine (1.5 mg/kg), the level of motor and locomotor activity significantly increased further in all the lines as compared to saline controls. The horizontal and vertical activities and the distance covered by rats of the high line, both at the baseline and after amphetamine challenge, were significantly higher than those of the low line animals in absolute scores but not as proportion of relevant saline controls. Since appetitive 50 kHz USVs and locomotor activity are both dependent on the activity of the dopamine system, it is concluded that selection of rats based on the expression of their positive emotional state is also selecting other features than vocalization, namely locomotor behavior. This may help explain why these animals are relatively resistant to depressogenic manipulations.
Brain Research, 1984
Rates of local cerebral glucose utilization were measured by means of the quantitative autoradiographic 2-[14C]deoxyglucose technique in conscious rats following the acute administration of o-amphetamine (0.2-5.0 mg/kg, i.v.). Changes in locomotor and stereotypic behavior in similarly treated rats were examined as well. Administration of low doses (0.2 and 0.5 mg/kg) of amphetamine resulted in increased locomotor activity, accompanied by elevations in glucose utilization limited mainly to the nucleus accumbens. A moderate dose of o-amphetamine (1.0 mg/kg) produced locomotion and stereotypic sniffing. Metabolic activity at this dose was increased in the nucleus accumbens, throughout neocortical areas, and in components of the extrapyramidal system. A high dose of amphetamine (5.0 mg/kg) produced stereotypic gnawing and licking and was associated with significant increases in glucose utilization in the extrapyramidal system, most prominently in the subthalamic nucleus.
Behavioural and biochemical effects of chronic amphetamine treatment in the vervet monkey
Psychopharmacology, 1982
Five vervet monkeys were administered increasing doses (4--12 mg/kg/day) of d-amphetamine over a period of 35 days. Three phases od behavioural change were discerned: phase 1 during which animals exhibited repetitive stereotyped action sequences with rapid head movements, occasional abnormal grooming, picking at the cage, hand-staring and snatching; phase 2 in which behaviour became progressively more restricted and animals became markedly unresponsive to auditory, visual and tactile stimuli; phase 3 was characterised by the abrupt development of gross over-responsiveness to environmental stimuli, ataxia and tremor. At post-mortem, by comparison with controls, amphetamine-treated monkeys showed marked depletions of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in corpus striatum and cerebral cortex and reductions in the activities of tyrosine hydroxylase and dopa decarboxylase in striatum. Turnover of these monoamines, assessed by high-performance liquid chromatography determinations of their respective metabolites, was also reduced. These findings are interpreted as evidence of monoamine neurone destruction, most severely in the case of DA neurones. Though there was a non-significant reduction in 3H-spiperone binding (reaching almost 50% in nucleus accumbens), numbers of receptors for the monoamines nA and 5-HT were not significantly changed, and the activities of the enzymes choline acetyltransferase and glutamine decarboxylase were similar in experimental and control animals. The contrast of these findings with those seen in post-mortem brains in schizophrenia is discussed.