[1] Conversely, reduced locomotor activity is observed in bipolar individuals on mood stabilizers[1] and may be a characteristic symptom of the inattentive type of ADHD[12] (ADHD-PI) and sluggish cognitive tempo.
[citation needed] Hyperlocomotion is induced by dopamine releasing agents (DRAs) and psychostimulants like amphetamine and methamphetamine.
[3][5] The dopamine reuptake inhibitors (DRIs) amineptine, bupropion, and nomifensine increase spontaneous locomotor activity in animals.
[3][5] Reversal of amphetamine- and NMDA receptor antagonist-induced stereotypies is also employed as a test of drug antipsychotic-like activity.
[3][5] Selective norepinephrine releasing agents (NRAs) include ephedrine, pseudoephedrine, phenylpropanolamine, levomethamphetamine, and D-phenylalaninol.
[22] A potential confounding factor with β-hydroxyamphetamines like phenylpropanolamine, ephedrine, and pseudoephedrine is that they have lower lipophilicity compared to their amphetamine counterparts, with consequent reduced capacity to cross the blood–brain barrier and produce central nervous system effects.
[37] Findings on the modulation of the ventral tegmental area by the noradrenergic locus coeruleus are mixed and suggestive of both excitatory and inhibitory roles.
[48] The drug did not increase locomotor activity at the assessed doses, in which brain dopamine release was not affected.
[48] In contrast to levomethamphetamine, dextromethamphetamine at the same doses increased brain levels of both norepinephrine and dopamine and induced dose-dependent hyperlocomotion.
[48] Relatedly, levomethamphetamine shows similar sympathomimetic effects as dextromethamphetamine but is substantially less potent as a psychostimulant in animals.
[49][50][51][48] As in rodents, levomethamphetamine showed reduced reinforcing and stimulant-like effects compared to dextromethamphetamine in rhesus monkeys.
[56][57][58][59][60] In addition, NRIs decrease amphetamine-, cocaine-, methylphenidate-, and phencyclidine (PCP)-induced hyperlocomotion in rodents.
[57] Similarly, norepinephrine transporter (NET) knockout mice had low basal locomotor activity.
[57] Certain serotonin releasing agents (SRAs), like MDMA and MDAI, though notably not others, like chlorphentermine, fenfluramine, and MMAI,[65][17][66] induce locomotor hyperactivity in animals.
[76][77][78] The locomotor hyperactivity produced by MDMA is fully attenuated by combined serotonin 5-HT1B and 5-HT2A receptor antagonism.
[86][85][87] In addition, the α1-adrenergic receptor antagonists prazosin and doxazosin reduce the psychostimulant and/or euphoric effects of MDMA in humans.
[86][91] Dopamine receptors also appear to be involved in MDMA-induced hyperlocomotion, although findings in this area, both in animals and humans, seem to be conflicting.
[86][92][93] In contrast to non-selective SRAs like MDMA, the highly selective SRA MMAI induces hypolocomotion in animals.
[78][96][97][71][66][94] Selective serotonin reuptake inhibitors (SSRIs) have been reported to have no effect or to increase locomotor activity, at least under certain circumstances like novel environments.
[97][57][58][60] However, in other studies, SSRIs have been reported to produce hypolocomotion, an effect that could be reversed by the serotonin 5-HT2C receptor antagonist SB-242084.
[102] The non-selective serotonin receptor agonists and serotonergic psychedelics LSD and DOI decrease locomotor activity in animals.
[105] 5-MeO-DALT dose-dependently increased locomotor activity but produced a sharp decrease at the highest tested dose.
[113][14][114][115][116][117][118][119] Less-selective serotonin 5-HT2A receptor antagonists, like trazodone, have been found to decrease locomotor and behavioral activity and to inhibit amphetamine-, cocaine-, and PCP-induced hyperactivity in animals similarly.
[126][127][128][129] The selective serotonin 5-HT2C receptor antagonist SB-242084 has been found to produce modest hyperlocomotion at high doses in rodents.
[134] Hyperlocomotion is induced by NMDA receptor antagonists and dissociative hallucinogens such as phencyclidine (PCP), ketamine, and dizocilpine (MK-801).
[137] Classical opioids or μ-opioid receptor agonists like morphine and fentanyl stimulate locomotor activity in rodents.
[152][168] The dual TAAR1 full agonist and serotonin 5-HT1 receptor modulator ulotaront did not affect dextroamphetamine-induced hyperlocomotion in rats.