The role of injection cues in the production of the morphine preexposure effect in taste aversion learning

Abstract

Given that the attenuating effects of LiCl preexposure on LiCl‐induced taste aversions have been reported to be controlled associatively, via injection‐related cues, the present experiment examined the effects of morphine exposure on morphine‐induced taste aversions to assess the generality of this control. Specifically, in Experiment 1 rats were exposed to morphine every other day for five exposures prior to aversion conditioning in which saccharin was paired with morphine (5 mg/kg) for five trials. Between preexposure and conditioning, rats were either injected with saline for eight consecutive days (extinction) or received no treatment. Morphine exposure attenuated the morphine CTA, an attenuation unaffected by saline injections (i.e., extinction of the morphine‐associated cues). Experiment 2 showed that increasing the number of extinction injections to 16 had no effect on morphine preexposure, although it was somewhat weakened in all preexposed groups due to the increased time between preexposure and conditioning. Unlike with LiCl, the attenuating effects of morphine preexposure in aversion learning are most likely controlled by nonassociative mechanisms, such as drug tolerance. Supported by a grant from the Mellon Foundation to ALR.

Adolescent rats fail to demonstrate a LiCl-induced pre-exposure effect: Implications for the balance of drug reward and aversion in adolescence

“…Further Adult Group V0.56 displayed a greater percent shift in consumption than did Group Adult L0.56. *p < 0.05 from vehicle conditioned group environments (and procedures) and have been argued to result from the blocking of taste avoidance conditioning by stimuli that were associated with the aversive effects of LiCl during drug pre-exposure (Braveman, 1979;Cole et al, 1996;Dacanay & Riley, 1982;Davis et al, 2010;de Brugada et al, 2003ade Brugada et al, , b, 2004de Brugada et al, , 2005Willner, 1978). In this context, it is interesting that LiCl-induced taste avoidance in the adolescent subjects was unaffected by LiCl pre-exposure.…”

“…This explanation may be particularly relevant to the US pre-exposure effect, given that the attenuation in taste avoidance conditioning following drug pre-exposure has been argued for some drugs, e.g., the emetic LiCl, to be a function of the association of various environmental or injection cues with the aversive effects of the drug (Braveman, 1979;Cole et al, 1996;Dacanay & Riley, 1982;Davis et al, 2010;De Brugada et al, 2003a, b, 2004Willner, 1978; for reviews and alternative interpretations for other drugs, see Randich & LoLordo, 1979;Riley & Simpson, 2001). That is, during drug pre-exposure the injection-related cues are paired with the drug's aversive effects and when taste avoidance conditioning is subsequently attempted in the presence of these stimuli, the association between the taste and the aversive effects is blocked.…”

Pre‐exposure to cocaine or morphine attenuates taste avoidance conditioning in adolescent rats: Drug specificity in the US pre‐exposure effect

“…For other drugs, for example, LiCl, the effects of drug pre‐exposure on taste avoidance conditioning appear associative in nature (Mikulka, Leard, & Klein, ; Willner, ). Under these conditions, during drug pre‐exposure environmental and handling cues surrounding the drug injection become associated with the drug's aversive effects and block subsequent conditioning to the novel taste (Davis, De Brugada, & Riley, ; De Brugada, González, & Cándido, , De Brugada, Gonzalez, & Candido, , De Brugada, Gonzalez, Gil, & Hall, ; Mikulka et al, ; Willner, ). Neither the non‐associative nor the associative perspective is sufficient to explain every instance of US pre‐exposure, and it appears that specific drugs produce effects of pre‐exposure by different mechanisms.…”

“…| 491 and block subsequent conditioning to the novel taste (Davis, De Brugada, & Riley, 2010;De Brugada, González, & Cándido, 2003a, De Brugada, Gonzalez, & Candido, 2003b, De Brugada, Gonzalez, Gil, & Hall, 2005Mikulka et al, 1977;Willner, 1978). Neither the nonassociative nor the associative perspective is sufficient to explain every instance of US pre-exposure, and it appears that specific drugs produce effects of pre-exposure by different mechanisms.…”

Long-term contextual memory in infant rats as evidenced by an ethanol conditioned tolerance procedure

“…This effect was only found in subjects trained during the third, but not the second postnatal week, and it is coherent with previous reports (Arias et al, 2012), suggesting that by this age this ethanol effect is either context-independent or it is mediated by cues other than the open field, such as handling or those related to the injection that were present at training and testing. This would not be surprising since drug effects can be effectively conditioned to injection cues (de Brugada et al, 2003, Davis et al, 2010 and various (proximal vs distant) contextual cues can exert differential levels of control over tolerance, at least in adult animals (Costanzo et al, 1995).…”