TABLE 1

Effects of DA-reactive drugs and hyperthermia on striatal microglial activation, peak core temperature, and striatal DA content

Mice (n = 3–8 mice/group) were treated as indicated, and 48 h later brains were taken for lectin histochemistry and stereological analysis or DA determinations as described under Materials and Methods. Core body temperature was monitored throughout treatment by telemetry, and the peak temperature achieved is reported for all treatment conditions except low ambient temperature.


Treatmenta

Pharmacological Property

Doseb

Microglial Cell Count

Striatal DA

Peak Body Temp.c
mg/kg/injection ng/mg °C
Control 4 ± 1 19.3 ± 0.71 37.8 ± 0.03
Methamphetamine DA nerve terminal damage 5 mg/kg 221 ± 11** 3.4 ± 0.53** 38.9 ± 0.09
MPTP DA nerve terminal and cell body damage 20 mg/kg 316 ± 9** 5.8 ± 0.62** 37.5 ± 0.10
Cocaine DAT and 5HTT blocker 10 mg/kg 14 ± 3 17.8 ± 0.92 37.9 ± 0.12
WIN 35,428 DAT blocker, cocaine analog 10 mg/kg 5 ± 0.6 19.2 ± 0.41 38.9 ± 0.25
Nomifensine DAT blocker 10 mg/kg 4 ± 0.5 16.7 ± 0.69 38.5 ± 0.27
SKF 82958 DA D1 receptor agonist 10 mg/kg 5 ± 0.6 16.4 ± 0.40 37.2 ± 0.25
Quinpirole DA D2 receptor agonist 10 mg/kg 7 ± 1.3 16.8 ± 0.64 38.3 ± 0.26
Apomorphine Mixed D1/D2 agonist 4 mg/kg 5 ± 1.3 19.9 ± 0.40 38.2 ± 0.10
DOI 5-HT2A agonist and hyperthermia 1 mg/kg 3 ± 0.4 19.1 ± 0.40 38.5 ± 0.23
Elevated ambient temperature Hyperthermia 38-40°C, 6 h sustained 18 ± 1.8 15.1 ± 1.2** 40.0 ± 0.20
Low ambient temperature
Prevents methamphetamine toxicity
10-12°C, 8 h sustained
2 ± 0.5
18.5 ± 0.85
Not recorded
  • 5HTT, 5-hydroxytryptamine (serotonin) transporter.

  • ** Values different from respective controls, p < 0.01 using Dunnett's multiple comparison test.

  • a Treatments were selected to mimic specific, isolated properties exerted by methamphetamine. With the exception of methamphetamine and MPTP, none of the remaining treatments is associated with toxicity to DA nerve terminals and none cause persistent depletion of striatal DA.

  • b Doses of all compounds intended to mimic indicated pharmacological properties of methamphetamine were selected from the published literature and were purposely chosen from among maximal doses for the desired effect. All injections were given on the treatment schedule used for methamphetamine (four i.p. injections of the indicated dose with 2-h intervals between injections).

  • c Data are presented as peak body temperature and indicate highest single body temperature measured during the treatment period, according to the method reported by Bowyer et al. (1994).