Studies indicate that nucleus accumbens (NAcc) dopamine neurotransmission is involved in the reinforcing and direct effects of cocaine. The present study was initiated to explore further the relationship of NAcc extracellular dopamine concentrations ([DA]e) and cocaine self-administration using a yoked littermate design. In the first experiment, one rat from each litter was trained to self-administer cocaine i.v. (SA: 0.33 mg/inf) under a fixed ratio 2 schedule, while a second rat received simultaneous infusions of cocaine yoked to the infusions of the SA (YC). NAcc [DA]e and cocaine concentrations ([COC]) were assessed during the test sessions using in vivo microdialysis combined with microbore HPLC procedures. [DA]e and [COC] were significantly elevated in the SA and YC groups during the self-administration session; however, [DA]e were greater in the SA group compared to the YC group in the first hour of the session, even though [COC] were not significantly different. On the following day, the rats previously allowed to self-administer cocaine were administered response-independent cocaine infusions yoked to the infusion pattern from the previous day. [DA]e were significantly elevated above baseline levels during the session but were significantly less than concentrations obtained when cocaine was self-administered by these subjects. [COC] during the sessions were not significantly different between the two days. Baseline [DA]e were not significantly different between the SA and YC groups or between Day 1 and Day 2. Furthermore, there was no significant difference in the in vitro probe recovery between one and two days following probe implantation. These results suggest that the context in which cocaine was administered significantly altered the neurochemical response to equivalent brain concentrations of cocaine. NAcc [DA]e was significantly increased when the delivery of cocaine infusions was contingent on the behavior of the rat, indicative of a role in the neural processes underlying cocaine reinforcement.

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The drug self-administration paradigm is routinely used to assess the abuse liability of psychoactive compounds. Investigations of the behavioral effects of drug use, however, often involve the response-independent (experiment-delivered) administration of the compound. It is frequently assumed that response-independent presentation of a compound has the same effects as response dependent deliveries. The present study examined directly the effects of response-dependent (self-administered) versus response-independent (experimenter-delivered) administration of cocaine on food intake and lethality. Littermate triads were exposed to either cocaine (0.33 mg/infusion) or saline using a yoked-box procedure. One member of the triad self-administered the drug under a fixed-ratio 2 schedule. The other two rats received response-independent infusions of either cocaine or saline. Groups of triads were exposed to two different cocaine access conditions. Daily sessions were terminated after 6 h for one group and after the delivery of 80 infusions for the other. The mean number of infusions delivered each session was 47 (+/- 12) and 70 (+/- 11), respectively, for the 6-h and 80-infusion condition. Under the 80-infusion condition, response-independent infusions of cocaine resulted in a significantly higher rate of mortality compared to littermates self-administering identical amounts of the drug. A fewer number of deaths occurred under 6-h condition; however, only rats exposed to response-independent infusions died under both access conditions. These data indicate that the presence or absence of response dependency can profoundly alter the lethal effects of cocaine.

We present a terrestrial record of stable carbon and oxygen isotopes from paleosol carbonate for climate interpretations between ca. 71.0 and 63.6 Ma. Isotopic ratios point to covarying and elevated atmospheric CO 2 pressures and temperatures between ca. 70.0 and 69.0 Ma and ca. 65.5 and 65.0 Ma. These two greenhouse episodes were characterized by atmospheric CO 2 levels between 1000 and 1400 ppmV (V = volume) and by mean annual temperatures in west Texas between 21 and 23 °C (~35°N paleo-latitude). Atmospheric CO 2 and temperature relations indicate that a doubling of pCO 2 was accompanied by an ~0.6 °C increase in temperature. A temperature gradient of ~0.4 °C per degree of latitude is proposed for North America across the Cretaceous-Tertiary boundary when comparing temperature proxies from west Texas with paleobotanical work in North Dakota. Our data demonstrate strong coupling between terrestrial climates and ocean temperatures that were possibly forced by Deccan trap volcanic degassing, leading to dramatic global climate changes.

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Paleosol-bearing alluvial strata of latest Cretaceous and earliest Tertiary age are continuously exposed along Dawson Creek, in Big Bend National Park, west Texas, U.S.A., and exhibit a three-tier hierarchy of depositional cyclicity. Meter-scale, fluvial aggradational cycles (FACs) occur as fining-upward successions that are gradationally overlain by paleosols or are sharply overlain by the coarsergrained base of the succeeding FAC without an intervening paleosol. FACs stack into decameter-scale, fluvial aggradational cycle sets (FAC sets) that also fine upward, and from base to top contain either a gradual upsection increase in soil maturity and soil drainage or a somewhat symmetrical pattern of increasing and decreasing paleosol maturity. Longer-period trends of FAC thickness, lithologic proportions, paleosol maturity, and paleosol drainage indicate that two complete, and two partial, hectometer-scale fluvial sequences occur within the study interval. From base to top, each sequence is characterized by an asymmetric increase and decrease in FAC thickness, a decrease in the proportion of sand-prone fluvial facies, an increase in paleosol maturity, and better paleosol drainage. Whereas FACs and FAC sets are interpreted to record cyclic episodes of channel avulsion and stability, and longer-term avulsive channel drift within the alluvial valley, respectively, fluvial sequences may coincide with third-order sea-level changes within the North American Western Interior Seaway. As such, the Cretaceous-Tertiary (K-T)transition within the Tornillo Basin may provide an example of megascale stratigraphic cyclicity that is controlled by eustatic sea level within a fully fluvial succession. Thickening and thinning successions of FACs record a third-order period of accelerating (transgressiveequivalent) and decelerating (highstand-equivalent) base-level rise, and subsequent base-level fall (falling stage-to lowstand-equivalent). Sequence boundaries are placed at the sharp inflection between thinning and thickening FACs. Sand-prone facies and immature, more poorlydrained paleosols are associated with the transgressive-equivalent portion of each sequence, and mudrock-dominated overbank facies and their associated mature, well-drained paleosols are associated with the highstand-and falling stage-equivalent.

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