Treatment with the atypical antipsychotic, olanzapine, prevents the expression of amphetamine-induced place conditioning in the rat.
Place conditioning (PC) experiments were conducted as a means to further elaborate the treatment potential of the atypical antipsychotic, olanzapine (OLZ), for stimulant abuse. The resulting preference/aversion provides an indirect measure of the incentive salience (i.e., euphoria/dysphoria) produced by a drug. Male Sprague-Dawley rats (n=48) were conditioned in two unique environments (i.e., vertical vs. horizontal stripped walls, large vs. small grid flooring) using injections (1.0 mg/kg ip) of either amphetamine (AMPH) or saline (SAL). On average, animals displayed a significant preference for the AMPH-paired location after 2.5 weeks of conditioning (five pairings each of AMPH and SAL). Once the preference was established, animals were pretreated (60 min) with a single dose of OLZ (0.0, 0.56, 1.0 or 1.5 mg/kg sc) given on the test (AMPH-free) day. For the following week's test, animals were injected with SAL (1.0 mg/kg ip) in an attempt to recapture the side preference exhibited before OLZ treatment. OLZ treatment prevented the expression of the AMPH-conditioned preference and reduced locomotor activity. Inhibition of preference resulted from the highest dose of OLZ (1.5 mg/kg), while the inhibition of locomotor activity occurred across all three doses. Additionally, while the effects on preference were no longer apparent by the SAL test the following week (reversible), the activity was still depressed during the SAL tests in animals that had experienced the highest dose of OLZ (1.5 mg/kg). Control experiments, in which OLZ was used as the conditioning drug, suggest that OLZ itself possesses no aversive effects in the PC paradigm, and may even produce a preference for the drug-paired chamber. Because the AMPH preference is dependent on dopamine (DA) release in the nucleus accumbens (NAcc), these experiments suggest that OLZ pretreatment interferes with the rewarding, as well as the subjective effects of AMPH.
Mechanic
Jordan A
JA
Psychobiology Laboratories, Department of Psychiatry and Behavioral Sciences, University of Oklahoma Health Sciences Center, 800 NE 15th Street, Oklahoma City, OK, USA. jordan.mechanic@roche.com
Maynard
Brian T
BT
Holloway
Frank A
FA
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001569:Benzodiazepines; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004347:Drug Interactions; D008297:Male; D000077152:Olanzapine; D010805:Physical Conditioning, Animal; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019966:Substance-Related Disorders / Q000517:prevention & control
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D001569:Benzodiazepines; D010890:Pirenzepine; D000661:Amphetamine; D000077152:Olanzapine