Hippocampus modulates the behaviorally‐sensitizing effects of nicotine in a rat model of novelty‐seeking: Potential role for mossy fibers

Abstract

Present experiments investigate interactions between a rat model of the novelty-seeking phenotype and psychomotor sensitization to nicotine (NIC) in adolescence, and the potential role of hippocampal mossy fibers in mediating the behaviorally-sensitizing effects of NIC. Outbred rats were phenotype-screened as high-responders (HR; locomotor reactivity to novelty score ranking in the upper third of the population) or low-responders (LR; locomotor reactivity to novelty score ranking in the lower third of the population). In Experiment 1, both phenotypes were trained with four NIC injections (at 3-d intervals on postnatal days 33-44), and lidocaine microinfusion was used to temporarily inactivate the hippocampal hilus at each NIC injection. Systemic saline and microinjection of artificial cerebral spinal fluid (CSF) were used as controls. During NIC training, lidocaine inactivation caused augmented locomotor response to NIC in HRs compared to LRs irrespective of injection days. Following 1 week of abstinence, all animals were challenged with a low dose of NIC. During challenge, previously NIC/CSF trained LRs and HRs were divided into two; one half receiving lidocaine inactivation of the hippocampal hilus and the other half receiving CSF control microinjection. Only HRs showed behavioral sensitization to the challenge dose of NIC, which was enhanced with lidocaine inactivation. In Experiment 2, a single NIC exposure was found sufficient to induce sensitization to the challenge dose of NIC in HRs, and concurrently an enlarged supra-pyramidal mossy fiber (SP-MF) terminal field. The increase in the SP-MF volume in HRs was greater with repeated NIC training. In both single and repeated NIC training cases, a significant positive morphobehavioral correlation was observed between challenge NIC-induced locomotion and the SP-MF terminal field volume. These findings suggest that the HR hippocampal mossy fibers are vulnerable to neuroadaptive alterations induced by NIC, which may be a substrate for the observed behavioral vulnerability to NIC.

Effects of a cannabinoid receptor (CB) 1 antagonist AM251 on behavioral sensitization to nicotine in a rat model of novelty-seeking behavior: correlation with hippocampal 5HT

“…The hippocampus is one such area that interacts with the mesolimbic reward circuitry (Brog et al 1993;Wright and Groenewegen 1995;Pierce et al 1998). We have shown that a single nicotine injection was sufficient to develop locomotor sensitization to a low-dose nicotine challenge following the injection-free period in HR animals, which was enhanced by lidocaine inactivation of the hippocampal hilus (Bhatti et al 2007). A positive correlation was observed between challenge nicotineinduced locomotion and the mossy fiber terminal field volume.…”

“…Food and water were available ad libitum. On PN 24, animals were screened for locomotor reactivity to a novel environment for 60 min using commercially available locomotion chambers (San Diego Instruments, San Diego, CA, USA; Bhatti et al 2007).…”

“…The LRHR phenotype is useful for predicting propensity to self-administer nicotine (Suto et al 2001). We have recently shown that adolescent HR rats show expression of behavioral sensitization to nicotine after a single nicotine exposure, and lidocaine inactivation of hippocampus enhances this behavior (Bhatti et al 2007).…”

Chaperone heat shock protein 70 in nucleus accumbens core: a novel biological target of behavioural sensitization to morphine in rats

“…Traditionally, behavioural sensitization was induced by repeated, intermittent drug exposures. Amazingly, even a single drug exposure, such as an exposure to amphetamine (Robinson et al, 1982;Vanderschuren et al, 1999), cocaine (Kalivas and Alesdatter, 1993), morphine (Vanderschuren et al, 2001;Jing et al, 2011;Luo et al, 2011;Qin et al, 2013) and nicotine (Bhatti et al, 2007) can also evoke behavioural sensitization. Although the extent of behavioural sensitization induced by a single drug exposure is not as profound as that induced by multiple drug exposures, the enduring behavioural and neurochemical consequences of single and repeated drug exposures appear to be highly comparable (Vanderschuren et al, 2001).…”

Cognitive mechanisms underlying relapse to nicotine

“…In addition, a variety of other chronic nicotine-induced changes, such as enhanced FosB (Soderstrom et al , 2007 ), decreased adult stem cells, coupled with increased cell death (Abrous et al , 2002 ) feature prominently in the granule cell layer of the DG. Other region-specifi c changes include mossy fi ber terminal sprouting and a role for these same axons in behavioral sensitization to nicotine, both of which are dependent on the baseline behavioral state of the animals (Bhatti et al , 2007 ).…”