A computerized apparatus designed to automatically dispense, measure, and record alcohol consumption by individual members of a rhesus macaque social group: trait-like drinking across social- and single-cage conditions.

BACKGROUND: The present study tested the validity of an automated ethanol dispensing apparatus that is capable of identifying individual monkeys and precisely measuring their levels of ethanol consumption while living in a social group, and assessed individual subjects' level of consumption when alone and in social groups. METHODS: In Experiment 1, 21 rhesus macaques (Macaca mulatta) were given access for 1-h each day to the dispensing apparatus, which contained an aspartame-sweetened 8.4% (v/v) ethanol solution. Measurements of blood ethanol concentrations were taken for each subject and compared with the level of consumption recorded by the apparatus for those subjects. To examine the possibility that competition among the animals limited their access to the dispensing unit, in Experiment 2, 10 of the subjects used in Experiment 1 were singly housed to allow them to drink without interference from other monkeys. A correlation was then performed to assess the interindividual relationship between the amount of ethanol consumed in these two housing conditions. RESULTS: In Experiment 1, the volume of solution measured and recorded by the apparatus correlated positively with the true volume dispensed. Furthermore, the volume of solution reported by the computer to have been consumed by an individual subject correlated positively with blood ethanol concentrations. In Experiment 2, the volume of ethanol consumed by individual subjects in single cages correlated positively with their consumption in the social group. CONCLUSIONS: The apparatus accurately identified and measured individual patterns of ethanol consumption among socially housed animals. Additionally, individual differences in ethanol consumption remained stable across settings, as shown by the strong positive correlation between drinking in a social setting versus drinking alone. This finding may thus reflect an individual's constitutional proclivity to consume alcohol.

Ultra-long antagonism of kappa opioid agonist-induced diuresis by intracisternal nor-binaltorphimine in monkeys.

Kappa opioid receptor (KOR) agonists such as U-50488H and bremazocine are analgesics and diuretics. In monkeys, the selective KOR antagonist, nor-binaltorphimine (nor-BNI), produces a long-lasting antagonism of the antinociceptive effects of U-50488H but not those of bremazocine, suggesting that KOR-mediated antinociception may occur through two distinct KORs. The aim of this study was to characterize the antagonist effect of nor-BNI against the diuretic effects of U-50488H and bremazocine in monkeys. Urine outputs were collected over 3 h subsequent to i.m. administration of KOR agonists. Both U-50488H (0.032-1 mg/kg) and bremazocine (0.00032-0.01 mg/kg) dose-dependently increased urine output and the diuretic effect reached a plateau at higher doses. The maximum effect of either U-50488H or bremazocine was approximately 15 ml/kg/3 h of urine. Pretreatment with intracisternal nor-BNI 0.32 mg significantly blocked both U-50488H (0.18 mg/kg)- and bremazocine (0.0032 mg/kg)-induced diuresis for 20 weeks. However, the same dose of nor-BNI 0.32 mg given subcutaneously was not effective. These results demonstrate that central KOR mediate KOR agonist-induced diuresis in monkeys. More important, this study provides functional evidence for a homogenous population of KOR underlying KOR-mediated diuresis and illustrates a unique pharmacological profile of nor-BNI-induced ultra-long KOR antagonism in vivo.

Ontogenetic adaptation and learning: a developmental constraint in learning for a thermal reinforcer.

Hoffman, Flory, and Alberts (1999) demonstrated that 1-, 5-, and 11-day-old rats in a cool environment (25 degrees C) acquired an operant head-turning response when rewarded with a 20-s warming of the platform on which they lay. In the current experiment 5- and 11-day-old rats in a hot environment (40 degrees C) acquired the head-turning response when rewarded with a 20-s cooling of the platform on which they lay, but 1-day-olds did not. The concept of ontogenetic adaptation helps us interpret these results: Neonatal thermotaxis constrains the 1-day-olds from learning a novel operant response for a cool reinforcer in a hot environment. Because the thermotaxis wanes from birth, it is not as strong in 5- and 11-day-old pups that are thus able to learn the operant for a cool reinforcer.

Neonatal thermotaxis improves reversal of a thermally reinforced operant response.

One-, 5-, and 11-day-old rats in a cool environment (25 degrees C) acquired an operant response when rewarded with a 20-s-long warming of the platform (from 25 to 36 degrees C) on which they lay. In Experiment 1, the head-turning response was learned by pups at all ages. When the contingency was reversed so that pups were reinforced for turning to the side opposite that correct during training, the original response extinguished for 1-day-olds, but not for 5- or 11-day-olds. In Experiment 2, the rewarded side was randomly selected for each trial. One-day-olds perseverated in turning to the side correct on that trial while the reinforcer remained on, but 5- and 11-day-old rat pups did not. We conclude that 1-day-old pups were more responsive to the change in experimental contingency in Experiment 1 due to this thermotaxic behavior.

Instrumental learning for a thermal reinforcer in 1-day-old rats.

One-day-old rats in a cool environment (25 degrees C) quickly acquired an instrumental response when rewarded with a 20-s warming of the platform (from 25 degrees C to 36 degrees C) on which they lay. The instrumental response, turning the head to one side, was learned within 30 min after the thermal contingency began and extinguished when the contingency was reversed. This experiment demonstrates rapid operant learning by neonates in a task that does not contain a Pavlovian stimulus-reinforcer contingency. The novel experimental method has wide applicability in psychology and neuroscience.

Amphetamine, cocaine, and dizocilpine enhance performance on a lever-release, conditioned avoidance response task in rats.

A lever-release version of the conditioned avoidance response (CAR) task was used to assess the behavioral effects of several psychomotor stimulants in rats. The indirect dopamine agonists, d-amphetamine (0.1 and 0.25 mg/kg) and cocaine (7.5 and 15 mg/kg), enhanced performance on this task. Both drugs increased percent avoidance responses and decreased avoidance latency. A higher dose of amphetamine (0.5 mg/kg) also decreased avoidance latency but failed to improve percent avoidance. Similar effects were seen at low (0.01 and 0.025 mg/kg) and high (0.05 mg/kg) doses of dizocilpine (MK-801), a stimulant that acts as a noncompetitive antagonist of N-methyl-d-aspartate (NMDA) glutamate receptors. When combined with haloperidol (0.1 mg/kg), a dopamine antagonist, amphetamine (0.25 mg/kg) and dizocilpine (0.025 mg/kg) had differential effects on the lever-release CAR task. Thus, amphetamine-haloperidol was significantly better than haloperidol alone on percent avoidance but not on avoidance latency, whereas dizocilpine-haloperidol had the opposite effect: significantly better than haloperidol alone on avoidance latency but not on percent avoidance. Taken together, these results provide further support for dopaminergic mechanisms in CAR performance but suggest an opposing glutamatergic influence.

Phencyclidine-induced increases in striatal neuron firing in behaving rats: reversal by haloperidol and clozapine.

Amphetamine and related drugs of abuse facilitate dopamine transmission in the striatum. This action is believed to underlie the increase in firing of striatal motor-related neurons after amphetamine administration in behaving rats. The present study extended this electrophysiological investigation to phencyclidine (PCP), a nonamphetamine psychomotor stimulant that acts primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) glutamate receptors. Like amphetamine, PCP (1.0, 2.5, or 5.0 mg/kg) increased the activity of striatal motor-related neurons concomitant with behavioral activation. These effects were blocked by subsequent administration of either 1.0 mg/kg haloperidol or 20.0 mg/kg clozapine, typical and atypical neuroleptics, respectively. Dizocilpine (MK- 801), another noncompetitive NMDA antagonist, mimicked the effect of PCP. Collectively, these results indicate that amphetamine and NMDA antagonists exert comparable effects on striatal motor-related neurons, suggesting that the response of these cells to psychomotor stimulants is regulated by a dopaminergic-glutamatergic influence.