Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats.
There is emerging evidence that the neuropeptide oxytocin may be utilised as a treatment for various psychopathologies, including drug addictions. Here we used an animal model to assess whether oxytocin might be effective in the treatment of methamphetamine addiction. Sprague-Dawley rats were trained to lever press to intravenously self-administer methamphetamine under a progressive ratio schedule of reinforcement. Once responding had stabilised, one group of rats received escalating doses of oxytocin (0.001, 0.01, 0.1, 0.3, 1 mg/kg) administered intraperitoneally (IP) prior to daily self-administration tests, while other rats received vehicle. After these tests, lever-pressing was extinguished and the ability of methamphetamine primes (IP, 1 mg/kg) to reinstate responding was studied with and without co-administration of oxytocin (IP, 0.3 and 1 mg/kg). Results showed that oxytocin dose-dependently reduced responding for intravenous methamphetamine with an almost complete absence of responding at the highest oxytocin dose (1 mg/kg). Hyperactivity during methamphetamine self-administration was also dose-dependently reduced by oxytocin. Oxytocin (1 but not 0.3 mg/kg) also reduced the ability of methamphetamine to reinstate methamphetamine-seeking behaviour. In separate tests, oxytocin (IP, 0.3 and 1 mg/kg) robustly decreased the hyperactivity and rearing induced by methamphetamine challenge (IP, 1 mg/kg), producing activity levels similar to control animals. This study suggests that oxytocin may have a powerful inhibitory effect on the motivation to consume methamphetamine and on hyperactivity associated with acute methamphetamine intoxication. These results point to the potential utility of human trials of oxytocin as a therapeutic treatment for methamphetamine addiction.
Carson
Dean S
DS
Brain and Mind Research Institute, University of Sydney, Australia.
Cornish
Jennifer L
JL
Guastella
Adam J
AJ
Hunt
Glenn E
GE
McGregor
Iain S
IS
D019969:Amphetamine-Related Disorders / Q000188:drug therapy / Q000209:etiology / Q000523:psychology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D010120:Oxytocics / Q000627:therapeutic use*; D010121:Oxytocin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D012646:Self Administration
D000697:Central Nervous System Stimulants; D010120:Oxytocics; D008694:Methamphetamine; D010121:Oxytocin