Effects of Estradiol on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

Abstract

The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E 2 b) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E 2 b in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose-effect curve determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17b-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E 2 b in cyclodextrin and in sesame oil were studied. Acute administration of E 2 b did not consistently alter the cocaine self-administration or drug discrimination dose-effect curves in comparison to saline control treatment. Females also did not selfadminister E 2 b (0.00001-0.10 mg/kg, i.v.) above saline levels. Finally, E 2 b (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys.

Effects of Progesterone and Testosterone on Cocaine Self-Administration and Cocaine Discrimination by Female Rhesus Monkeys

“…Estradiol enhanced cocaine self-administration in gonadally intact rodents (Roberts et al, 1989;Hecht et al, 1999;Lynch et al, 2002) and in ovariectomized rodents (Lynch et al, 2001;Hu et al, 2004;Jackson et al, 2006). However, other studies report that estradiol did not enhance cocaine self-administration in rodents (Caine et al, 2004;Lynch and Taylor, 2005) or in female rhesus monkeys (Mello et al, 2008). Although species and procedural variables contribute to these discrepant findings, the unit dose of cocaine used to maintain self-administration appears to be one critical variable (Mello et al, 2008).…”

“…However, other studies report that estradiol did not enhance cocaine self-administration in rodents (Caine et al, 2004;Lynch and Taylor, 2005) or in female rhesus monkeys (Mello et al, 2008). Although species and procedural variables contribute to these discrepant findings, the unit dose of cocaine used to maintain self-administration appears to be one critical variable (Mello et al, 2008). At cocaine doses that maintained robust self-administration, it has been difficult to detect any effect of estradiol (Caine et al, 2004;Lynch and Taylor, 2005;Mello et al, 2008).…”

“…to determine if hormone levels remained elevated for the duration of the cocaine self-administration and cocaine discrimination sessions described below. Samples for analyses were collected at 5-min intervals for 120 min in three awake gonadally intact female monkeys using procedures described previously (Mello et al, 1993(Mello et al, , 2008.…”

“…Although species and procedural variables contribute to these discrepant findings, the unit dose of cocaine used to maintain self-administration appears to be one critical variable (Mello et al, 2008). At cocaine doses that maintained robust self-administration, it has been difficult to detect any effect of estradiol (Caine et al, 2004;Lynch and Taylor, 2005;Mello et al, 2008).…”

Long-Term Parenteral Administration of 2-Hydroxypropyl-β-Cyclodextrin Causes Bone Loss

“…Based on its favorable chemical properties, HP-b-CD has been used as a vehicle for oral and parenteral administration of several drugs in animals and humans (Leeson et al 2007;Tansho et al 2006), and especially for administration of steroid hormones in different fields of research (Kan et al 2008;Mello et al 2008;Rabbani et al 1997). Sex steroids play a major role in skeletal development and maintenance (Erben et al 2004;Lapauw et al 2009;Vandenput et al 2001).…”