Multidimensional behavioral analyses show dynorphin A-(1-13) modulation of methamphetamine-induced behaviors in mice.

The effects of intracerebroventricular (i.c.v.) injection of dynorphin A-(1-13) on methamphetamine-induced behavioral alterations in mice were determined by using multidimensional behavioral analyses. Methamphetamine (0.3, 1.0 and 3.0 mg/kg s.c.) produced a marked increase in linear locomotion, circling, rearing and/or grooming behaviors. The behavioral effects of methamphetamine (1.0 mg/kg s.c.) were almost completely antagonized by pretreatment with the dopamine D2 receptor antagonist, S(-)-sulpiride (3.0 and/or 10.0 mg/kg i.p.), but not with the dopamine D1 receptor antagonist, SCH 23390 (0.01 or 0.03 mg/kg i.p.). Although dynorphin A-(1-13) (3.0 or 12.5 micrograms i.c.v.) alone did not produce any significant effects on behavior, the methamphetamine (1.0 mg/kg s.c.)-induced increase in circling ipsilateral to the injection side was markedly enhanced by dynorphin A-(1-13) (12.5 micrograms i.c.v.). In contrast, the peptide (12.5 micrograms i.c.v.) inhibited the methamphetamine (1.0 mg/kg s.c.)-induced increase in rearing, whilst the increase in grooming remained unchanged. The effects of dynorphin A-(1-13) (12.5 micrograms i.c.v.) were fully reversed by the opioid antagonist, Mr 2266 (5.6 mg/kg s.c.). These results suggest that the unilateral administration (i.c.v.) of dynorphin A-(1-13) inhibits the activity of dopamine-elicited neurotransmission, resulting in an increase in ipsilateral circling and in a decrease in rearing.