US Preexposure

Preexposures to a drug can attenuate CTAs induced by pairing a novel flavor with the drug as US. This US preexposure effect has been reported for a variety of drugs {Gamzu, 1977 #1688}, including LiCl {Riley, 1976 #1736}{Suarez, 1976 #1737}{Braveman, 1975 #1734}{Revusky, 1975 #1733}, cyclophosphamide {Elkins, 1974 #1010}, apomorphine {Brookshire KH, 1976 #1735}, and morphine {Dacanay, 1982 #1727}. Generally, a relatively large number of preexposures is required to cause attenuation of a subsequent CTA, e.g. 5-8 injections of the drug across multiple days. The effect of US preexposure to attenuate subsequent induction of a CTA by the US is variable and dependent upon the class of drug and the experimental protocol {Dacanay, 1982 #1727}. Two mechanisms have been proposed to explain the US preexposure effect: i) the development of physiological tolerance or habituation to the effects of the US, or ii) blocking of the CTA by the association of the US with ambient environmental cues during preexposure trials in the absence of the conditioned taste stimulus.

In the case of LiCl, physiological tolerance or habituation does not appear to occur. Across repeated injections of LiCl, there is no attenuation of unconditioned responses such as decreased locomotor activity and hypothermia across 8 injections {Batson, 1983 #1731} or enhanced neophobia after 3 injections {de Brugada, 2003 #1732}. However, there is evidence that injections of LiCl become associated with the cues of a test environment {Dacanay, 1982 #1727} or injection procedure {de Brugada, 2005 #1730;de Brugada, 2004 #1729}, so associative blocking may contribute more to any LiCl preexposure event. '

Notes:

Elkins 1974 6 preexposure injections of cyclophosphamide reduced cond. flavor aversion, but 3 pre-exposures failed.

Revusky and Kaukulis 1975 8 pre-exposures to either oral 10% ethanol or ip. injection o 1.2ml or 2% LiCl Result: increased rat of extinction of lithium induced taste aversion to oral ethanol

Braveman 1975 1 or 3 pre-injections of 10 ml/kg of 0.3 M LiCl

Riley 1976 Six injections of 0.15M LiCl, 12 ml/kg at 96 hour intervals Result blocked iniital saccharin/LiCl CTA in one bottle tests, but overcome with multiple pairings

Suarez 1976 Preexposure: 6 LiCl injections ( 0.12 M, 20 ml/kg) at 72 h intervals Result: attenuated one-bottle saccharin CTA

Brookshire and Brackbill 1976 10 preconditioning injections of apomorphine blocked apo-induced favlor aversion.

Batson and Best 1979 -- too complicated to cite

Best and Domjan 1979 single injection of LiCl given proximal to conditioning (i.e. 30 min before trial) attenuates CTA, but not if given 24 h before conditioning.

Dacany and Riley 1982 5 injections of LiCl paired with novel environment atteniuated CTA induced with LiCl in novel environment; 5 injections of morphine attenuated morphine induced CTA in both novel environment and home cagte, so probably tolerance. [they mention several other drugs that have preexposure effect -- effects of US prexposure and role of associative blocking or tolerance may be drug and protocol specific].

Batson 1983 8 injections of LiCl 12 ml/kg, 0.15 M at 48 h intervals. no sign of tolerance or habituation to effects of LiCl on temperature or activity

Misanin and Hinderliter -- lots of papers on us prexposiure

Debrugda et al 2003 3 injections of 0.15M LiCl, 20 ml/kg at 48 h intervals, Result: did not attenuate LiCl induced neophobia (i.e. decreased intake of a novel saccharin solution).

Debrugda et al 2004, Debrugada 2005 (cite both papers, which have similar conclusions) 3 LiCl injections attenuated sucrose CTA paired with Licl injection but no oral CTA induced by drinking LiCl solution; therefore evidence for blocking of cues.

Papers to Find: cited by Batson & Best 1979: , Gamzu 1977 in the Learned aversions book, Holman 1976,