Naive Rhesus Research Articles

Intratracheal inoculation of human varicella zoster virus (VZV; MAV strain) vaccine successfully induced VZV IgG antibodies in rhesus monkeys

BackgroundThe objective of this study was to investigate whether the use of live attenuated varicella zoster virus (VZV) MAV vaccination can efficiently induce VZV antibody production in naive rhesus monkeys as an approach to prevent simian varicella virus (SVV) reactivation in animals immunosuppressed for transplantation studies.ResultsClinically available human VZV vaccine was used to induce the production of anti-VZV antibodies in rhesus monkeys. A vial of the vaccine was subcutaneously injected at 0 week, and the second and third vaccination was performed at 5 and 6 weeks by intratracheal inoculation. The titer of anti-VZV IgG was assessed at 0, 2, 4, 6, and 7 weeks. At 2 weeks, 3/16 were seropositive for VZV IgG. At 6 weeks, 9/16 were shown to be seropositive. At 7 weeks, 16/16 were found to be seropositive.ConclusionsThe VZV vaccine via intratrachael inoculation was shown to induce VZV IgG humoral immunity in rhesus monkeys and may be important immunosuppressed macaques for transplantation studies. Although the humoral immunity produced is an important finding, further studies will be necessary to confirm possible protection and it could protect probably against SVV infection in rhesus monkey.

Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use

Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1h/day), following 60 sessions under extended-access conditions (4h/day), and following 4weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.

Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity

A common viral immune evasion strategy involves mutating viral surface proteins in order to evade host neutralizing antibodies. Such immune evasion tactics have not previously been intentionally applied to the development of novel viral gene delivery vectors that overcome the critical problem of anti-vector immunity. Recombinant, replication-incompetent adenovirus serotype 5 (rAd5) vector-based vaccines for human immunodeficiency virus type 1 and other pathogens have proved highly immunogenic in preclinical studies but will probably be limited by the high prevalence of pre-existing anti-Ad5 immunity in human populations, particularly in the developing world. Here we show that rAd5 vectors can be engineered to circumvent anti-Ad5 immunity. We constructed novel chimaeric rAd5 vectors in which the seven short hypervariable regions (HVRs) on the surface of the Ad5 hexon protein were replaced with the corresponding HVRs from the rare adenovirus serotype Ad48. These HVR-chimaeric rAd5 vectors were produced at high titres and were stable through serial passages in vitro. HVR-chimaeric rAd5 vectors expressing simian immunodeficiency virus Gag proved comparably immunogenic to parental rAd5 vectors in naive mice and rhesus monkeys. In the presence of high levels of pre-existing anti-Ad5 immunity, the immunogenicity of HVR-chimaeric rAd5 vectors was not detectably suppressed, whereas the immunogenicity of parental rAd5 vectors was abrogated. These data demonstrate that functionally relevant Ad5-specific neutralizing antibodies are focused on epitopes located within the hexon HVRs. Moreover, these studies show that recombinant viral vectors can be engineered to circumvent pre-existing anti-vector immunity by removing key neutralizing epitopes on the surface of viral capsid proteins. Such chimaeric viral vectors may have important practical implications for vaccination and gene therapy.

Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys

A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

ACQUISITION OF COCAINE SELF-ADMINISTRATION WITH UNSIGNALED DELAYED REINFORCEMENT IN RHESUS MONKEYS

Six experimentally naive rhesus monkeys produced 0.01 mg/kg/infusion cocaine by lever pressing under a tandem fixed-ratio 1 differential-reinforcement-of-other-behavior schedule. One lever press initiated an unsignaled 15- or 30-s delay culminating in cocaine delivery. Each press made during the delay reset the delay interval. With two exceptions, responding was acquired and maintained at higher rates than responding on a second (inoperative) lever. For the exceptions, a cancellation contingency was arranged in which each formerly inoperative-lever response reset the tandem schedule. This manipulation reduced presses on the inoperative lever. Subsequently, the consequences of responding on the two levers were reversed, and the monkeys again responded at higher rates on the operative lever. As a comparison, 3 additional experimentally naive monkeys received response-independent cocaine deliveries. Although lever pressing was observed, it extinguished and was subsequently reestablished under the tandem schedule. The results suggest that although response-reinforcer contiguity is not required for cocaine to acquire reinforcing functions, a response-reinforcer relation appears necessary.

Serial expertise of rhesus macaques.

Here we describe the development of serial expertise in 4 experimentally naive rhesus monkeys that learned, by trial and error, the correct order in which to respond to 3-, 4-, and 7-item lists of arbitrarily selected photographs. The probabilities of guessing the correct sequence on 3-, 4-, and 7-item lists were, respectively, 1/6, 1/24, and 1/5,040. Each monkey became progressively more efficient at determining the correct order in which to respond on new lists. During subsequent testing, the subjects were presented with all possible pairs of the 28 items used to construct the four 7-item lists (excluding pairs of items that occupied the same ordinal position in different lists). Subjects responded to pairs from different lists in the correct order 91% of the time on the first trials on which these pairs were presented. These features of subjects' performance, which cannot be attributed to procedural memory, satisfy two criteria of declarative memory: rapid acquisition of new knowledge and flexible application of existing knowledge to a new problem.

Excitotoxic Lesions of the Amygdala Fail to Produce Impairment in Visual Learning for Auditory Secondary Reinforcement But Interfere with Reinforcer Devaluation Effects in Rhesus Monkeys

Aspiration lesions of the amygdala were found previously to produce a severe impairment in visual discrimination learning for auditory secondary reinforcement in rhesus monkeys (Gaffan and Harrison, 1987). To determine whether excitotoxic amygdala lesions would also produce this effect, we trained four naive rhesus monkeys on the same task. The monkeys were required to learn 40 new visual discrimination problems per session in a situation in which visual choices were guided by an auditory secondary reinforcer that had been previously associated with food reward. Bilateral excitotoxic lesions of the amygdala had no effect on the rate of learning visual discrimination problems for auditory secondary reinforcement. We also tested the amygdalectomized monkeys on a reinforcer devaluation task and compared their performance with a group of three normal monkeys. The monkeys first learned to discriminate 60 pairs of objects, baited with two different food rewards. Each of the food rewards was then devalued by selective satiation in two separate experimental sessions. Normal controls tended to avoid displacing objects that covered the devalued food to a significantly greater degree than did the amygdalectomized monkeys, indicating that the excitotoxic amygdala damage interfered with reinforcer devaluation effects. Our results are consistent with the idea that the amygdala is necessary for learning the association between stimuli and the value of particular food rewards; however, the amygdala is not necessary for maintaining the value of secondary reinforcers, once they have been learned.

Experimental Measles. II. Infection and Immunity in the Rhesus Macaque

Measles infection and the host immune response to measles virus were compared using naive and immunized rhesus monkeys. The monkeys were experimentally challenged with a wild-type strain of measles virus inoculated intranasally. After pathogenic virus challenge, measles virus was detected in mononuclear cells of peripheral blood, lymph node, and spleen in naive monkeys and viremia peaked on Day 7. However, only one of five vaccinated monkeys had a low virus titer in peripheral blood mononuclear cells at one time point after challenge. No virus was detected in the lymphoid tissues from an immunized monkey that was euthanized on Day 7 of infection. Measles-specific IgM, IgG, neutralizing antibody, and cytotoxic T lymphocytes were detected in vaccinated monkeys before challenge, but antibody titers were significantly lower in immunized monkeys than in naive monkeys after challenge. Measles-specific IgG antibody and cytotoxic T cell responses were still detected more than 1 year after vaccination or infection. This animal model is useful for the further study of measles pathogenesis, immunosuppression, and immunologic memory.

Immune Complexes Bound to the Primate Erythrocyte Complement Receptor (CR1) via Anti-CR1 Mabs Are Cleared Simultaneously with Loss of CR1 in a Concerted Reaction in a Rhesus Monkey Model

In the circulation of primates, C3b-opsonized immune complexes (IC) bound to erythrocyte (E) CR1 are taken to the liver and spleen where IC are removed and destroyed without lysis or sequestration of E. Individuals with diseases associated with IC processing often have decreased E CR1 levels, and in previous primate animal models of IC disease, E CR1 was shown to be reduced, but the relationship between IC processing and CR1 loss remained to be clarified. We have developed a simple model to study this question. In naive (nonimmunized) rhesus monkeys, E-bound mouse anti-CR1 mAbs (1500 IgG/E) are not rapidly cleared from the circulation. Infusion of monkey anti-mouse IgG leads to rapid indirect binding of this second antibody to E CR1. Subsequently, in what appears to be a concerted reaction, CR1-bound nascent IC are rapidly cleared from the circulation and CR1 is removed from E at the same rate. Clearance of bound IC and loss of CR1 were both independently followed by RIA. Imaging studies localized the cleared anti-CR1 mAbs to the liver. Western blots indicated that the loss of CR1 was not due to a conformational change, and E CR1 levels returned to normal in 2–3 weeks, suggesting that the return was associated with synthesis of new E. Our findings suggest that the key step in the clearance mechanism requires recognition (possibly by Fc receptors) of IC-like material associated with E CR1, and this leads to loss of CR1 and uptake of the CR1-IC substrate by liver phagocytic cells.

A chimeric simian/human immunodeficiency virus expressing a primary patient human immunodeficiency virus type 1 isolate env causes an AIDS-like disease after in vivo passage in rhesus monkeys

The utility of the simian immunodeficiency virus of macaques (SIVmac) model of AIDS has been limited by the genetic divergence of the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and the SIVs. To develop a better AIDS animal model, we have been exploring the infection of rhesus monkeys with chimeric simian/human immunodeficiency viruses (SHIVs) composed of SIVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rev. SHIV-89.6, constructed with the HIV-1 env of a cytopathic, macrophage-tropic clone of a patient isolate of HIV-1 (89.6), was previously shown to replicate to a high degree in monkeys during primary infection. However, pathogenic consequences of chronic infection were not evident. We now show that after two serial in vivo passages by intravenous blood inoculation of naive rhesus monkeys, this SHIV (SHIV-89.6P) induced CD4 lymphopenia and an AIDS-like disease with wasting and opportunistic infections. Genetic and serologic evaluation indicated that the reisolated SHIV-89.6P expressed envelope glycoproteins that resembled those of HIV-1. When inoculated into naive rhesus monkeys, SHIV-89.6P caused persistent infection and CD4 lymphopenia. This chimeric virus expressing patient isolate HIV-1 envelope glycoproteins will be valuable as a challenge virus for evaluating HIV-1 envelope-based vaccines and for exploring the genetic determinants of HIV-1 pathogenicity.

Effects of different food-reinforcement histories on cocaine self-administration by rhesus monkeys

The purpose of the present study was to examine whether a history of responding under food reinforcement schedules that generated either high or low response rates would influence the acquisition and maintenance of cocaine self-administration. Eight experimentally naive rhesus monkeys were initially trained to respond on the right lever under either a fixed-ratio (FR) 50 or interresponse times (IRT) > 30-s schedule of food reinforcement. After 65 sessions of food-maintained responding, monkeys were surgically prepared with indwelling intravenous catheters and cocaine 0.03 mg/kg per injection (IV) was available on the left lever under a fixed-interval (FI) 5-min schedule. After at least 60 consecutive sessions at this dose, a cocaine dose-response curve (saline, 0.01-0.3 mg/kg per injection) was determined. The FR 50 schedule generated high rates of food-maintained responding (90.1 +/- 6.2 responses/min), while response rates under the IRT > 30-s schedule were low (1.9 +/- 0.1 responses/min). Across the 60 consecutive sessions under the FI 5-min schedule, linear changes in response rates and cocaine intake were significantly different between FR- and IRT-history monkeys. FR-history monkeys responded at higher rates than IRT-history subjects, while cocaine intake during the first 15 sessions was lower in FR- compared to IRT-history monkeys. Rates of cocaine-maintained responding after food-reinforcement histories were compared to response rates of monkeys initially trained to self-administer cocaine under an FI 5-min schedule (Nader and Reboussin 1994).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of behavioral history on cocaine self-administration by rhesus monkeys.

The purpose of the present study was to examine whether a history of responding under schedules that generate either high or low response rates could modify previously established cocaine self-administration. Eight experimentally naive rhesus monkeys were trained to respond on one of two levers under a fixed-interval (FI) 5-min schedule of intravenous cocaine (0.03 mg/kg per injection) presentation. When responding was stable a cocaine dose-response curve (saline, 0.01-0.3 mg/kg per injection) was determined. Following completion of the dose-response curves, the monkeys were randomly assigned to one of two groups (n = 4/group) and trained to respond on the other lever under either a fixed-ratio (FR) 50 or inter-response times (IRT) > 30-s schedule of cocaine (0.03 mg/kg per injection) presentation. After 65 sessions responding was again maintained under the FI5-min schedule of 0.03 mg/kg per injection cocaine for 60 sessions, followed by redetermination of the cocaine dose-response curve. During the initial exposure to the FI schedule, the mean rate of responding was 4.02 (+/- 0.33) responses/min and the cocaine dose-response curve was characterized as an inverted-U shape function of dose, with peak responding at 0.03 mg/kg per injection. The FR50 schedule generated high rates (66.80 +/- 5.6 responses/min), while response rates under the IRT > 30-s schedule were low (2.62 +/- 0.2 responses/min). Following different behavioral histories, response rates under the FI5-min schedule were significantly higher for 60 sessions in FR-history monkeys compared to IRT-history subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Removal of the amygdala plus subjacent cortex disrupts the retention of both intramodal and crossmodal associative memories in monkeys.

Naive rhesus monkeys (Macaca mulatta) were trained preoperatively in an automated test apparatus on an auditory-visual (crossmodal) conditional task or on a visual-visual (intramodal) conditional task that involved learning a fixed set of stimulus-stimulus associations or paired associates. After having learned their respective tasks, each monkey received bilateral removal of the amygdala plus subjacent cortex. The 2 experimental groups showed equally poor retention of the stimulus-stimulus associations and subsequently relearned their respective crossmodal and intramodal associations at the same rate. These data argue against the idea that the amygdala is specialized for crossmodal associations. Instead, the data indicate that the amygdala or its underlying cortex, or both, play a more generalized role in stimulus-stimulus associative memory.

Passively transferred antibodies directed against conserved regions of SIV envelope protect macaques from SIV infection.

Inactivated plasma collected from either SIV-infected or peptide-vaccinated macaques was transferred into 17 naive rhesus monkeys. Two additional macaques received normal plasma and served as controls. Following transfer all 19 monkeys were inoculated with SIV. While the controls became infected and were virus-isolation-positive, 3 of 6 recipients of SIV peptide vaccine plasma and 9 of 11 recipients of SIV-infected monkey plasma were protected. None of the 12 protected animals became virus-isolation-positive or seroconverted within 100 days of follow-up. One, however was SIV-PCR-positive. All 12 protected animals were rechallenged 100 days after the initial inoculation; 8 became infected and yielded virus as expected, but 4 remained uninfected. One of the latter was the SIV-PCR-positive monkey mentioned above, suggesting that cryptic SIV infection may be of significance in immunological protection. The results demonstrate that envelope anti-peptide antibodies have similar protective potential in vivo as antibodies directed to the whole virus. In vitro neutralization competition assays performed with sera from vaccinated macaques in the presence of the free peptides suggest that of the four conserved envelope peptides of the vaccine, the two originating from gp41 rather than the two from gp120 are responsible for inducing the neutralizing anti-syncytial activity.

Failure of intravenous pentagastrin challenge to induce panic-like effects in rhesus monkeys

We examined the ability of intravenous (i.v.) challenge with pentagastrin to induce behavioural and cardiovascular effects consistent with panic attack in conscious rhesus monkeys. For behavioural evaluation, 4 naive male rhesus monkeys familiar with minimal manual restraint necessary for drug administration received a rapid i.v. bolus of pentagastrin (4, 8 or 16 μg/kg) or water on four separate occasions according to a randomised cross-over design. Behaviour was rated by a blind observer continuously during, and for the first 5 min immediately following i.v. injections while the monkey sat on the handler's lap, and then for a further 25 min in an individual observation cage. In separate experiments, the ability of pentagastrin to alter cardiovascular parameters which may accompany panic or anxiety (elevated heart rate and blood pressure) was explored. For cardiovascular studies, 8 male or female rhesus monkeys with femoral artery catheters were chair restrained and received a bolus injection of pentagastrin (4, 8 or 16 μg/kg) or saline into the saphenous vein at 30 min intervals. Blood pressure and heart rate were monitored continuously using a Statham Gould pressure transducer. Pentagastrin induced no consistent behavioural or cardiovascular changes. Similar pilot studies using CCK 4 also failed to reveal such effects. We conclude that CCK-induced panic-like effects may not be demonstrable following challenge with pentagastrin under laboratory conditions in rhesus monkeys.

Immunization with lentivirus-like particles elicits a potent SIV-specific recall cytotoxic T-lymphocyte response in rhesus monkeys.

An effective acquired immunodeficiency syndrome (AIDS) vaccine should be capable of eliciting human immunodeficiency virus (HIV)-specific cytotoxic T-lymphocyte (CTL) responses. We have explored the use of lentivirus-like particles produced in mammalian cells infected with a recombinant vaccinia virus to immunize for the induction of CTL in the simian immunodeficiency virus (SIV)/rhesus monkey model for AIDS. SIV-like particles in a threonyl-MDP-based adjuvant did not elicit a high frequency of SIV gag-specific effector cells in naive rhesus monkeys. However, immunization with these particles elicited a potent recall CTL response in monkeys previously vaccinated with a recombinant vaccinia-SIV virus. These observations suggest that poxvirus-produced virus-like particles may represent a safe immunogen for use in periodic boosting to maintain viable cell-mediated immunity to the AIDS virus.

Ethanol-reinforced responding of naive rhesus monkeys: Acquisition without induction procedures

Rodents will typically consume greater amounts of low concentration ethanol (1–6%) than water. However, few primate oral self-administration studies have examined low ethanol concentrations. Additionally, there is a scarcity of data showing ethanol-maintained behavior without using induction procedures in either rats or primates. In this study, 14, free-feeding, naive, adult, male rhesus monkeys were given access to a 2% (w/v) ethanol solution and vehicle (tap water) during daily 3-hour sessions. Water was freely available between sessions. Liquids were available under a concurrent fixed-ratio four reinforcement schedule; thus, four responses (mouth-spout contacts) on either spout were immediately followed by the delivery of approximately 0.65 ml of liquid. In phase 1, tap water was available from both spouts. In phase 2, vehicle and a 2% ethanol solution were concurrently available. The 2% ethanol solution maintained considerably higher response rates than vehicle for 12 of 14 monkeys. In phase 3, food intake was limited. During this phase, the 2% ethanol solution maintained significantly higher response rates than vehicle for all monkeys. Additionally, during phase 3, ethanol intakes were greater than those in phase 2 for all monkeys. Central drug effects and taste factors are discussed. These results demonstrate that ethanol will serve as a reinforcer for naive rhesus monkeys in the absence of induction procedures.

Removal from natal social group to peer housing affects cortisol levels and absolute numbers of T cell subsets in juvenile rhesus monkeys

Psychosocial stress associated with the removal of six naive juvenile rhesus monkeys from their natal social group to peer housing resulted in increased basal cortisol secretion and significant decrements in the absolute numbers of the T lymphocyte subsets in the peripheral blood. Six subjects matched for age and social rank remained in the group of 80 animals serving as controls. Baseline immune and cortisol measurements were obtained before the six test subjects were removed from the group and housed together in an outdoor circular enclosure. Blood samples were taken 24 h following removal of the test subjects from the group and at intervals thereafter through 11 weeks. Compared to controls, test subjects showed a significant decrease in the absolute numbers of CD4 + (−56.9%) and CD8 + T cells (−57.6%) and a significant increase in basal cortisol levels (+43.9%) 24 h following removal to peer housing. Group difference in the absolute numbers of most immune cells persisted through 11 weeks, whereas cortisol differences lasted only through 2 weeks. These data, when compared to an earlier study employing an identical protocol, with the exception that subjects were housed in indoor individual cages following separation, fail to demonstrate a modulating effect of randomly chosen peer-mates on the stress effects produced by social separation.

Social separation and reunion affects immune system in juvenile rhesus monkeys

Removal of juvenile rhesus monkeys from their natal social group to indoor individual caging resulted in increased basal cortisol secretion and significant decrements in the frequency of lymphoid subpopulations. Fourteen juvenile rhesus monkeys, which had never been removed from the group, were studied. Baseline immune and cortisol measurements were obtained before seven of the subjects were removed from social housing to standard individual cages. The remaining seven subjects, matched for age, sex, weight, and rank, remained in the social group throughout the study serving as controls. Blood samples were taken 24 hours after removal of the test subjects from the group and at specific intervals thereafter through 11 weeks. At 24 hours after the separation test subjects showed a significant increase in basal cortisol levels (40%) and a significant decrease in several immune parameters, with absolute numbers of total T cells declining 72 ± 12%. Significant group differences in immune parameters persisted through 11 weeks. Eighteen weeks following removal, the test subjects were returned to the group which produced a cortisol rise in both test and controls at the 24-hour postreturn sample. Although there were no group differences in the frequency of lymphoid subsets 24 hours after return, some test subjects showed marked decrements which were inversely related to cortisol and were predicted by behavioral events. These data demonstrate that the removal of naive juvenile rhesus monkeys from their natal social group to individual indoor caging is a potent psychosocial stressor and that the behavioral interactions which characterize the return of the individual subjects to the natal group may predict physiological response.

The Effect of Desglycinamide‐(ARG8)‐Vasopressin (DGAVP) on the Acquisition of Free‐Choice Alcohol Drinking in Rhesus Monkeys

The vasopressin analog desglycinamide-(Arg8)-vasopressin (DGAVP) has been reported to reduce the acquisition of heroin and cocaine self-injection behavior in rats. This led to the hypothesis that DGAVP can reduce the self-administration of psycho-active drugs (including ethanol) by attenuating central reinforcement processes. Under forced ingestion conditions, DGAVP has been reported, however, to enhance alcohol drinking in rats. We studied the effect of DGAVP on the acquisition of voluntary, free-choice alcohol drinking in naive rhesus monkeys, that had concurrent access to either 1% and 2% (n = 12) or to 4% and 8% (n = 8) ethanol/water solutions in addition to drinking water. Half of the monkeys were injected twice per day with 50 micrograms.kg-1 of DGAVP for 14 successive days, the other half received placebo. Subsequently, all subjects had access to the same solutions for another 14 days without treatment. DGAVP did not significantly affect concentration preference behavior. With regard to net ethanol ingestion in animals drinking 1% and 2% solutions, DGAVP decreased net ethanol intakes, having a time-dependent and long lasting effect; placebo-treated animals gradually increased net ethanol intakes over time. The placebo-treated animals in the 4% and 8% group, showed a different acquisition pattern; DGAVP reduced net ethanol intake in two animals in a similar way as above. Two animals behaved differently. It is concluded that in a free-choice condition DGAVP did not enhance the acquisition of alcohol drinking in monkeys, but rather inhibited ethanol self-administration in the majority of the subjects.