Estrogen improves response accuracy and attenuates the disruptive effects of delta9-THC in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance.

Despite evidence of an interaction between cannabinoids and estrogen in the brain, little information is available regarding the consequences of this interaction on behavior. A within-subjects design was used to examine the effects of estrogen and delta9-tetrahydrocannabinol (delta9-THC) on learning and memory in ovariectomized rats responding under a multiple schedule of repeated acquisition and performance. Treatment with low physiological levels of estrogen, delivered in Silastic capsules, improved response accuracy without affecting response rate during acquisition. Estrogen also attenuated the ability of delta9-THC (0.56- 3.2 mg/kg) to decrease response accuracy and rate during acquisition and response accuracy during performance. Results indicate that estrogen can improve accuracy during acquisition of a nonspatial operant task and can attenuate delta9-THC- induced behavioral deficits.

Alcohol unmasks simian immunodeficiency virus-induced cognitive impairments in rhesus monkeys.

BACKGROUND: Alcohol and human immunodeficiency virus (HIV) produce similar neuropathological profiles, including loss of neurons in the frontal cortex. Additionally, HIV-positive patients with a history of alcohol abuse have greater neurologic deficits, and chronic alcohol abuse produces electrophysiological deficits earlier in the HIV disease process. Few studies, preclinical or clinical, have examined whether alcohol administration exacerbates the neuropsychological deficits in subjects with lentiviruses such as HIV. METHODS: To examine the combined effects of alcohol and immunodeficiency viruses (IVs) on neuropsychological functioning, four groups of young adult rhesus monkeys trained to respond under two complex behavioral tasks were administered ethanol 4 days per week via an intragastric catheter for 3 months and then infected with simian immunodeficiency virus (SIV). Behavioral testing after SIV inoculation was conducted in each group (-ethanol [EtOH]/-SIV, -EtOH/+SIV, +EtOH/-SIV, and +EtOH/+SIV) on days when alcohol was not administered to avoid a direct confound and on several occasions when ethanol or sucrose was administered as a probe of the effect of alcohol alone and the effect of caloric supplementation on the food-maintained tasks, respectively. RESULTS: During the days of the week when ethanol was not administered, little or no disruption was observed in either response rate or the percentage of errors (accuracy) across the different treatment groups. In contrast, behavioral testing during alcohol administration revealed that subjects in the various treatment groups had different susceptibilities to ethanol administration. As expected, a two-way ANOVA (ethanol condition, SIV condition) indicated there were significant main effects of ethanol on both response rate and percent errors in both behavioral tasks, but it also indicated there was a significant interaction between ethanol administration and SIV infection on the accuracy of responding in the acquisition (learning) task. In addition, the main effect of SIV on percent errors was in the performance task. CONCLUSIONS: The fact that alcohol administration in SIV-infected monkeys produced greater behavioral deficits than either alcohol or SIV alone further strengthens the supposition that IVs adversely affect neural substrates involved in cognition and that the adverse effects of many central nervous system drugs may be enhanced in IV-infected individuals.