Pretreatment with nomifensine or nomifensine analogue 4-phenyl-1,2,3,4-tetrahydroisoquinoline augments methamphetamine-induced stereotypical behavior in mice

Abstract

Nomifensine is a dopamine/norepinephrine reuptake inhibitor. Nomifensine and some of its structural analogues produce behavioral effects indicative of indirect dopaminergic agonist properties, such as hyperlocomotion. By contrast, the deaminated and demethylated nomifensine analogue 4-phenyl-1,2,3,4-tetrahydroisoquinoline (PTIQ) is reported to have amphetamine-antagonistic properties, as demonstrated by inhibition of methamphetamine (METH)-induced dopamine release in the nucleus accumbens and METH-induced hyperlocomotion in rats. In the present study, we examined the effect of PTIQ (10 mg/kg, i.p.) and nomifensine (3 mg/kg, i.p.) on METH (5 or 10 mg/kg ,i.p.)-induced stereotypical behavior in mice in order to determine whether PTIQ and nomifensine inhibit and augment, respectively, METH-induced stereotypical behavior. Unexpectedly, our observations demonstrated that both PTIQ and nomifensine significantly augmented METH-induced stereotypical behavior and locomotion in mice. This augmentation is likely the result of additive effects on dopaminergic function by METH in combination with PTIQ or nomifensine. These results suggest that, contrary to some reports, PTIQ may display dopaminergic agonist properties in mice.

Pretreatment or Posttreatment with Aripiprazole Attenuates Methamphetamine-induced Stereotyped Behavior in Mice

“…For instance, about only 30% of mice exhibited maximal expression levels of stereotypy when 5 mg/kg of METH was administered. 43 Since the intention of this study was to examine individual components of METH-induced stereotypy, a higher (ie, 10 mg/kg) dose was used. Aripiprazole was dissolved in vehicle solution, ie, sterile saline containing 2% Tween 80 (SigmaUltra grade)/0.5% carboxymethyl cellulose sodium salt (Sigma-Aldrich, St. Louis, MO, USA).…”

“…Since individual stereotypical behaviors were unchanged for long periods (>30 seconds) after drug treatment, it was possible to record the observations by hand. The behaviors scored were inactive (awake and inactive, or sleeping), ambulation, rearing, persistent locomotion, head bobbing (up-and-down movements of the head), continuous sniffing, circling, and continuous nail and/or wood chip biting or licking, according to a method described previously 43 Ambulation, rearing, and persistent locomotion were considered locomotor and exploratory behaviors, and the last four categories were considered stereotypies. Persistent locomotion was not classified as stereotypy because the mice scored as having “persistent locomotion” showed horizontal locomotor activity less than or equal to that displayed by mice showing “hyperlocomotion” induced by 1 mg/kg METH (which is not generally defined as a stereotypy) measured by Animex Auto.…”

“…METH was dissolved in sterile saline and the injection dose was 10 mg/kg. 42,43 METH-induced stereotypy is dose-dependent; lower doses stimulate locomotion but do not produce stereotypical behavior. For instance, about only 30% of mice exhibited maximal expression levels of stereotypy when 5 mg/kg of METH was administered.…”

Lithium for schizophrenia: supporting evidence from a 12-year, nationwide health insurance database and from Akt1-deficient mouse and cellular models

“…Methamphetamine-induced locomotion and stereotypic behavior were modified and conducted as previously described 77 . Briefly, to assess methamphetamine-induced stereotypic behavior and spontaneous locomotor activity, we placed each mouse into an open-field apparatus (25.40 × 25.40 × 40.64 cm 3 , Coulbourn Instruments, Whitehall, PA, USA) under dim lighting conditions (60 lx).…”

Brain Histamine N-Methyltransferase as a Possible Target of Treatment for Methamphetamine Overdose

“…16,25,26 For instance, a single administration of METH at doses of 0.5–2 mg/kg induces hyperlocomotion, 16,27–30 while rodents exhibit stereotypy when treated with higher doses of METH (5–20 mg/kg). 31–37 Rodents exhibiting stereotypy after acute high doses of METH are considered to be a model for METH overdose. To evaluate METH-induced stereotypy reproducibly, Tatsuta et al developed an experimental procedure using mice as follows 35 : test subjects are placed in a transparent acrylic box (30 × 30 × 35 cm) with ~25 g of fresh wood chips spread on the floor of the chamber and observed for stereotypy for one hour after drug challenge by observers unaware of the treatments.…”