Dopamine motor activity

Dopamine. Dopamine (DA) (2) is an intermediate in the synthesis of NE and Epi from tyrosine. DA is localized to the basal ganglia of the brain and is involved in the regulation of motor activity and pituitary hormone release. The actions of DA are terminated by conversion to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase-A and -B (MAO-A and -B) in the neuron following reuptake, or conversion to homovanillic acid (HVA) through the sequential actions of catechol-0-methyl transferase (COMT) and MAO-A and -B in the synaptic cleft. 

Figure 7.8 Dopamine and motor function. When nigrostriatal dopamine activity is normal so is motor function. Any reduction in this DA activity, as in Parkinson s disease, results in reduced motor activity, i.e. akinesia. By contrast, too much DA activity, as in Huntington s Chorea, produces abnormal motor function, i.e. dyskinesia. The latter may be controlled by neuroleptic drugs (DA antagonists) but they can swing the balance in DA activity sufficiently to produce akinesia (Parkinsonism). DA agonists (and levodopa) may overcome akinesia but can induce DA overactivity and dyskinesia (peak dose effect) (see Chapter 15)...

The most consistent and potent antagonism of amphetamine effects on increased motor activity and stereotyped movements is obtained with antagonists at dopamine receptors of the D2 subtype (Creese et al. 1982). This is not the case with amphetamine s disruptive effects on social and aggressive behavior. So far, no antagonists have been identified that reverse amphetamine s disruption of sexual, play, maternal, or aggressive behavior. 

Opioid receptor antagonists have been found to modulate brain dopamine-mediated behavioral and cellular functions such as motor activity, drug selfadministration, and brain stimulation reward (Koob and Bloom 1988). 

The motor activation produced by psychomotor stimulants has been long associated with the midbrain dopamine systems. While focused stereotyped behavior produced by high doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the corpus striatum (Creese and Iversen 1975), the locomotor activation produced by low doses of indirect sympathomimetics is blocked by removal of dopamine terminals in the region of the nucleus accumbens (Kelly et al. 1975). This dopaminergic substrate for psychostimulant effects appears selective for the indirect sympathomimetics in that dopamine lesions to the region of the nucleus... 

RESPONSE Yes, it means that the animal is capable of moving around for apomorphine. But then it gets subtle. In people, too, there is initially a high level of activity to exhaust residual dopamine stores and then the activity goes down to a very low level. The apomorphine can reinstate some locomotion. I think the most convincing evidence is the heroin. It is not true motor activity. 

Stimulants theoretically exert their effect by blocking the reuptake of dopamine and norepinephrine, thus improving academic performance and decreasing motor activity in ADHD patients. Stimulants have been shown to decrease fidgeting and finger tapping, increase on-task classroom behavior and positive interactions at home and in social environments, and ameliorate conduct and anxiety disorders.14... 

Bruinink A., Lichtensteiger W., Schlumpf M. (1983). Ontogeny of diurnal rhythms of central dopamine, serotonin and spirodecanone binding sites and of motor activity in the rat. Life Sci. 33(1), 31-8. 

O Neill R. D., Fillenz M. (1985). Simultaneous monitoring of dopamine release in rat frontal cortex, nucleus accumbens and striatum effect of drugs, circadian changes and correlations with motor activity. Neuroscience 16(1), 49-55. 

Paulson P. E., Robinson T. E. (1994). Relationship between circadian changes in spontaneous motor activity and dorsal versus ventral striatal dopamine neurotransmission assessed with on-line microdialysis. Behav. Neurosci 108(3),... 

Heikkila, R.E., Cabbat, F.S., and Duviosin, R.C., Motor activity and rotational behavior after analogs of cocaine correlation with dopamine uptake blockade, Commun. Psychopharm., 3, 285, 1979. 

Lazarini CA, Florio JC, Lemonica IP et al (2001) Effects of perinatal exposure to deltamethrin on forced swimming behavior, motor activity, and striatal dopamine levels in male and female rats. Neurotoxicol Teratol 23 665-673... 

Baldo BA, Sadeghian K, Basso AM, Kelley AE. 2002. Effects of selective dopamine D1 or D2 receptor blockade within nucleus accumbens subregions on ingestive behavior and associated motor activity. Behav Brain Res 137(1-2) 165-177. 

Cronan T, Conrad J, et al (1985) Effects of chronically administered nicotine and sahne on motor activity in rats. Pharmacol Biochem Behav 22(5) 897-899 Curtis L, Buisson B, et al (2002) Potentiation of human alpha4beta2 neuronal nicotinic acetylcholine receptor by estradiol. Mol Pharmacol 61(1) 127-135 Dalton JC, Vickers GJ, et al (1986) Increased self-administration of cocaine following haloperidol sex-dependent effects of the antiestrogen tamoxifen. Pharmacol Biochem Behav 25(3) 497-501 Damsma G, Day J, et al (1989) Lack of tolerance to nicotine-induced dopamine release in the nucleus accumbens. Eur J Pharmacol 168(3) 363-368 Di Chiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85(14) 5274-5278... 

Kelley, A. F. and Lang, C. G. 1989. Effects of GBR 12909, a selective dopamine uptake inhibitor, or motor activity and operant behaviour in the rat. European Journal of Pharmacology, 167 385-395. 

Mechanism of Action A CNS stimulant that blocks the reuptake of norepinephrine and dopamine into presynaptic neurons, increasing the release of these neurotransmitters into the synaptic cleft. Therapeutic Effect Decreases motor restlessness and fatigue increases motor activity, mental alertness, and attention span elevates mood. 

Mechanism of Action An amphetamine that enhances the action of dopamine and norepinephrine by blocking their reuptake from synapses also inhibits monoamine oxidase and facilitates the release of catecholamines. Therapeutic Effect Increases motor activity and mental alertness decreases motor restlessness, drowsiness, and fatigue suppresses appetite. 

Rossetti ZL, Pani L, Kuzmin A, et al Dihydropyridine calcium antagonists prevent cocaine-, but not amphetamine-, induced dopamine release and motor activity in rats. Acta Physiol Hung 75 (suppl) 249-250, 1990 Rossetti ZL, Lai M, Hmaidan Y, et al Depletion of mesohmbic dopamine during behavioural despair partial reversal by chronic imipramine. Eur J Pharmacol 242 313-315, 1993... 

FIGURE 12-3. When (/-amphetamine binds to the presynaptic dopamine transporter on the dopamine neuron, it not only blocks dopamine reuptake but actually causes dopamine release. There may be a preference or selectivity for cortical over striatal dopamine presynaptic terminals by (/-amphetamine, so lower doses may have preferential effects on attention rather than on motor activity. Methylphenidate has a similar action, which is not quite as rapid but longer-lasting in many patients. 

When making a choice of test situations, some investigators are biased by the effects of the tested substance in adulthood. Based on this knowledge, it is possible to formulate and test a specific hypothesis about aspects of brain and behavioral development that are expected to be affected. For instance, haloperidol can be expected to alter development of the dopamine system and motor activity, whereas clonidine can be expected to affect development of the catecholamine system and REM sleep. 

De Souza Silva, M., Topic, B., Huston, J. and Mattern, C. (2008) Intranasal dopamine application increases dopaminergic activity in the neostriatum and nucleus accumbens and enhances motor activity in the open field. Synapse 62, 176-184. 

---