Oxytocin and vasopressin modulation of social anxiety following adolescent intermittent ethanol exposure.

RATIONALE: Adolescent intermittent ethanol exposure (AIE) produces lasting, sex-specific social anxiety-like alterations in male, but not female rats. Oxytocin (OXT) and vasopressin (AVP) brain systems play opposite roles in regulating social preference/avoidance, with OXT increasing approach to, and AVP increasing avoidance of social stimuli. OBJECTIVES: To test the hypothesis that social anxiety-like alterations seen in adult males after AIE are associated with a shift in the balance between OXT and AVP toward AVP, effectiveness of pharmacological activation of the OXT system and blockade of endogenous activity at AVP receptors for reversing AIE-induced social anxiety-like alterations was assessed, along with examination of the effects of AIE on OXT, vasopressin V1a, and V1b receptor (OXT-R, V1a-R, and V1b-R) surface expression in the hypothalamus. METHODS: Sprague-Dawley male and female rats were given 4 g/kg ethanol (AIE) or water intragastrically every 48 h for a total of 11 exposures during postnatal days (P) 25-45. On P70-72, animals were given a social interaction test following administration of a selective OXT-R agonist WAY-267464, selective V1a-R antagonist SR-49059, or V1b-R antagonist SSR-149415, and hypothalamic tissue was collected. RESULTS: Social anxiety-like behavior was induced by AIE in males but not females, and was selectively reversed by the selective OXT-R agonist and V1b-R antagonist, but not V1a-R antagonist. AIE was also found to decrease OXT-R, but increase V1b-R neuronal surface expression relative to water-exposed controls in the hypothalamus of males, but not females. CONCLUSIONS: These findings demonstrate that AIE induces changes in OXT-R and AVP-R surface expression in the hypothalamus along with social anxiety-like alterations in male rats. These social anxiety-like alterations can be reversed either by activation of the OXT system or by suppression of the AVP system, data that support the hypothesis that social anxiety-like alterations induced by adolescent alcohol exposure in male rats are associated at least in part with an OXT/AVP imbalance.

Impairment of the anterior thalamic head direction cell network following administration of the NMDA antagonist MK-801.

Head direction (HD) cells, found in the rodent Papez circuit, are thought to form the neural circuitry responsible for directional orientation. Because NMDA transmission has been implicated in spatial tasks requiring directional orientation, we sought to determine if the NMDA antagonist dizocilpine (MK-801) would disrupt the directional signal carried by the HD network. Anterior thalamic HD cells were isolated in female Long-Evans rats and initially monitored for baseline directional activity while the animals foraged in a familiar enclosure. The animals were then administered MK-801 at a dose of .05 mg/kg or 0.1 mg/kg, or isotonic saline, and cells were re-examined for changes in directional specificity and landmark control. While the cells showed no changes in directional specificity and landmark control following administration of saline or the lower dose of MK-801, the higher dose of MK-801 caused a dramatic attenuation of the directional signal, characterized by decreases in peak firing rates, signal to noise, and directional information content. While the greatly attenuated directional specificity of cells in the high dose condition usually remained stable relative to the landmarks within the recording enclosure, a few cells in this condition exhibited unstable preferred directions within and between recording sessions. Our results are discussed relative to the possibility that the findings explain the effects of MK-801 on the acquisition and performance of spatial tasks.