title: 8-OH DPAT can restore the locomotor stimulant effects of cocaine blocked by haloperidol.
abstract: In the first experiment, separate groups of rats (n = 7) were treated with either saline, cocaine (10 mg/kg), haloperidol (0.1 mg/kg), or cocaine (10 mg/kg) plus haloperidol (0.1 mg/kg). Locomotor behavior was measured in an open-field environment, and cocaine induced a reliable locomotor stimulant effect compared to saline-treated animals. Haloperidol produced a progressive decline in locomotion over the 5 test days. Haloperidol also blocked cocaine stimulant effects compared to cocaine-treated animals. In the second experiment, five groups (n = 7) of animals were treated either with saline, cocaine (10 mg/kg), 8-OH DPAT (0.2 mg/kg), 8-OH DPAT (0.2 mg/kg) plus haloperidol (0.1 mg/kg), or 8-OH DPAT (0.2 mg/kg) plus haloperidol 0.1 mg/kg plus cocaine (10 mg/kg). Over the course of 5 days of treatment, cocaine induced a locomotor stimulant effect. Saline and 8-OH DPAT animals did not differ in terms of locomotion. The 0.1 mg/kg haloperidol plus 0.2 mg/kg 8-OH DPAT treatment decreased locomotion compared to the saline group, but the group given 0.2 mg/kg 8-OH DPAT plus 0.1 mg/kg haloperidol plus cocaine (10 mg/kg) exhibited a locomotor stimulant effect equivalent to the cocaine group. In a third experiment, it was found that the 0.2 mg/kg 8-OH DPAT treatment did not enhance the locomotor stimulant effect of cocaine. Thus, the 8-OH DPAT treatment was able to restore a cocaine locomotor stimulant effect in animals treated with haloperidol without directly enhancing the locomotor stimulant effects of cocaine. In Experiments 2 and 3, entries into the central zone of the open field were measured. Cocaine reliably increased central zone entries. The 8-OH DPAT treatment, however, selectively blocked this behavioral effect of cocaine suggesting a qualitative influence of 5-HT(1A) receptors upon cocaine, independent of locomotion activation by cocaine. Ex vivo measurements of dopamine and 5-hydroxytryptamine metabolism in limbic tissue were consistent with the established effects of cocaine, haloperidol, and 8-OH DPAT upon dopamine and 5-hydroxytryptamine neurotransmission. In addition, measurement of cocaine brain concentration indicated that neither haloperidol or 8-OH DPAT affected cocaine concentration in brain.
authors.affiliation: VA Medical Center, Syracuse, NY 13210, USA.
authors.forename: R
authors.initials: R
authors.lastname: Carey
authors.forename: E
authors.initials: E
authors.lastname: Damianopoulos
authors.forename: G
authors.initials: G
authors.lastname: De Palma
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006220:Haloperidol / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D018765:Dopamine Uptake Inhibitors; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003042:Cocaine; D006220:Haloperidol; D004298:Dopamine